Hydrocephalus can be defined broadly as a disturbance of formation, flow, or absorption of cerebrospinal fluid (CSF) that leads to an increase in volume occupied by this fluid in the central nervous system (CNS). This condition also could be termed a hydrodynamic disorder of CSF. Acute hydrocephalus occurs over days, subacute over weeks, and chronic over months or years. Conditions such as cerebral atrophy and focal destructive lesions also lead to an abnormal increase of CSF in CNS. In these situations, loss of cerebral tissue leaves a vacant space that is filled passively with CSF. Such conditions are not the result of a hydrodynamic disorder and therefore are not classified as hydrocephalus. An older misnomer used to describe these conditions was hydrocephalus ex vacuo.
Normal pressure hydrocephalus (NPH) describes a condition that rarely occurs in patients younger than 60 years. Enlarged ventricles and normal CSF pressure at lumbar puncture (LP) in the absence of papilledema led to the term NPH. However, intermittent intracranial hypertension has been noted during monitoring of patients in whom NPH is suspected, usually at night. The classic Hakim triad of symptoms includes gait apraxia, incontinence, and dementia. Headache is not a typical symptom in NPH.
Benign external hydrocephalus is a self-limiting absorption deficiency of infancy and early childhood with raised intracranial pressure (ICP) and enlarged subarachnoid spaces. The ventricles usually are not enlarged significantly, and resolution within 1 year is the rule.
Communicating hydrocephalus occurs when full communication exists between the ventricles and subarachnoid space. It is caused by overproduction of CSF (rarely), defective absorption of CSF (most often), or venous drainage insufficiency (occasionally).
Noncommunicating hydrocephalus occurs when CSF flow is obstructed within the ventricular system or in its outlets to the arachnoid space, resulting in ventricular/subarachnoid space noncommunication.
Obstructive hydrocephalus results from obstruction of the flow of CSF (intraventricular or extraventricular). Most hydrocephalus is obstructive, and the term is used to contrast the hydrocephalus caused by overproduction of CSF.
Arrested hydrocephalus is defined as stabilization of known ventricular enlargement, probably secondary to compensatory mechanisms. These patients may decompensate, especially following minor head injuries.
Pathophysiology
Normal CSF production is 0.20-0.35 mL/min; a majority is produced by the choroid plexus, which is located within the ventricular system, mainly the lateral and fourth ventricles. The capacity of the lateral and third ventricles in a healthy person is 20 mL. Total volume of CSF in an adult is 120 mL.
Normal route of CSF from production to clearance is the following: From the choroid plexus, the CSF flows to the lateral ventricle, then to the interventricular foramen of Monro, the third ventricle, the cerebral aqueduct of Sylvius, the fourth ventricle, the 2 lateral foramina of Luschka and 1 medial foramen of Magendie, the subarachnoid space, the arachnoid granulations, the dural sinus, and finally into the venous drainage.
ICP rises if production of CSF exceeds absorption. This occurs if CSF is overproduced, resistance to CSF flow is increased, or venous sinus pressure is increased. CSF production falls as ICP rises. Compensation may occur through transventricular absorption of CSF and also by absorption along nerve root sleeves. Temporal and frontal horns dilate first, often asymmetrically. This may result in elevation of the corpus callosum, stretching or perforation of the septum pellucidum, thinning of the cerebral mantle, or enlargement of the third ventricle downward into the pituitary fossa (which may cause pituitary dysfunction).
The mechanism of NPH has not been elucidated completely. Current theories include increased resistance to flow of CSF within the ventricular system or subarachnoid villi; intermittently elevated CSF pressure, usually at night; and ventricular enlargement caused by an initial rise in CSF pressure; the enlargement is maintained despite normal pressure because of the Laplace law. Although pressure is normal, the enlarged ventricular area reflects increased force on the ventricular wall.
Frequency
United States
Incidence of congenital hydrocephalus is 3 per 1,000 live births, while the incidence of acquired hydrocephalus is not known exactly.
International
Incidence of acquired hydrocephalus is unknown. About 100,000 shunts are implanted each year in the developed countries, but little information is available for other countries.
Mortality/Morbidity
In untreated hydrocephalus, death may occur by tonsillar herniation secondary to raised ICP with compression of the brain stem and subsequent respiratory arrest.
Shunt dependence occurs in 75% of all cases of treated hydrocephalus and in 50% of children with communicating hydrocephalus.
Patients are hospitalized for scheduled shunt revisions or for treatment of shunt complications or shunt failure.
Poor development of cognitive function in infants and children, or loss of cognitive function in adults, can complicate untreated hydrocephalus. It may persist after treatment.
Visual loss can complicate untreated hydrocephalus and may persist after treatment.
Sex
Generally, incidence is equal in males and females. The exception is Bickers-Adams syndrome, an X-linked hydrocephalus transmitted by females and manifested in males. NPH has a slight male preponderance.
Age
Incidence of human hydrocephalus presents a bimodal age curve. One peak occurs in infancy and is related to the various forms of congenital malformations. Another peak occurs in adulthood, mostly resulting from NPH. Adult hydrocephalus represents approximately 40% of total cases of hydrocephalus.
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Sunday 29 June 2008
Friday 27 June 2008
Treadmill and Pharmacologic Stress Testing
Cardiovascular exercise stress testing in conjunction with an ECG has been established as one of the focal points in the diagnosis and prognosis of cardiovascular disease, specifically coronary artery disease (CAD).
Feil and Seigel first noticed the significance of cardiovascular exercise stress testing in 1928; they reported ST and T changes following exercise in 3 patients with chronic stable angina.1 The following year, Master and Oppenheimer introduced a standardized exercise protocol to assess functional capacity and hemodynamic response.
Continued research into causal mechanisms of ST displacement, refinement of exercise protocols, and determination of diagnostic and prognostic exercise variables in clinical patient subsets have continued to evolve since 1929.
After the establishment of coronary angiography as a diagnostic tool, the limitation of exercise-induced ST-segment depression as a diagnostic marker for obstructive CAD in patient populations with a low disease prevalence became apparent.
Introduction
Exercise testing is a cardiovascular stress test using treadmill bicycle exercise with ECG and blood pressure monitoring. Pharmacologic stress testing, established after exercise testing, is a diagnostic procedure in which cardiovascular stress induced by pharmacologic agents is demonstrated in patients with decreased functional capacity or in patients who cannot exercise. Pharmacologic stress testing is used in combination with imaging modalities such as radionuclide imaging and echocardiography.
Exercise stress testing, which is now widely available at a relatively low cost, is currently used most frequently to estimate prognosis and determine functional capacity, to assess the probability and extent of coronary disease, and to assess the effects of therapy. Ancillary techniques, such as metabolic gas analysis, radionuclide imaging, and echocardiography, can provide further information that may be needed in selected patients, such as those with moderate or prior risk.
Exercise physiology
The initiation of dynamic exercise results in increases in the ventricular heart rate, stroke volume, and cardiac output due to vagal withdrawal and sympathetic stimulation. Also, alveolar ventilation and venous return increase as a result of sympathetic vasoconstriction. The overall hemodynamic response depends on the amount of muscle mass involved, exercise efficiency, conditioning, and exercise intensity.
In the initial phases of exercise in the upright position, cardiac output is increased by an augmentation in stroke volume mediated through the use of the Frank-Starling mechanism and heart rate. The increase in cardiac output in the later phases of exercise is due primarily to an increase in ventricular rate.
During strenuous exertion, sympathetic discharge is maximal and parasympathetic stimulation is withdrawn, resulting in autoregulation with generalized vasoconstriction, except in the vital organs (cerebral and coronary circulations).
Venous and arterial norepinephrine release from sympathetic postganglionic nerve endings is increased, and epinephrine levels are increased at peak exertion, resulting in an increase in ventricular contractility. As exercise progresses, skeletal muscle blood flow increases; oxygen extraction increases as much as 3-fold; peripheral resistance decreases; and systolic blood pressure (SBP), mean arterial pressure, and pulse pressure usually increase. Diastolic blood pressure (DBP) remains unchanged or may increase or decrease by approximately 10 mm Hg. The pulmonary vascular bed can accommodate as much as a 6-fold increase in cardiac output, with only modest increases in pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure; this is not a limiting determinant of peak exercise capacity in healthy subjects.
The maximum heart rate and cardiac output are decreased in older individuals, related in part to decreased beta-adrenergic responsiveness. Maximum heart rate can be calculated by subtracting the patient's age (y) from 220 (has a standard deviation of 10-12 beats per minute [bpm]). The age-predicted maximum heart rate is a useful measurement for safety reasons and as an estimate of the adequacy of the stress to evoke inducible ischemia. A patient who reaches 80% of the age-predicted maximum is considered to have a good test result, and an age-predicted maximum of 90% or better is considered excellent.
In the postexercise phase, hemodynamics return to baseline within minutes of discontinuing exercise. The return of vagal stimulation is an important cardiac deceleration mechanism after exercise and is more pronounced in well-trained athletes but blunted in patients with chronic congestive heart failure. Intense physical work or important cardiorespiratory impairment may interfere with achievement of a steady state, and an oxygen deficit occurs during exercise. The oxygen debt is the total oxygen uptake in excess of the resting oxygen uptake during the recovery period.
Feil and Seigel first noticed the significance of cardiovascular exercise stress testing in 1928; they reported ST and T changes following exercise in 3 patients with chronic stable angina.1 The following year, Master and Oppenheimer introduced a standardized exercise protocol to assess functional capacity and hemodynamic response.
Continued research into causal mechanisms of ST displacement, refinement of exercise protocols, and determination of diagnostic and prognostic exercise variables in clinical patient subsets have continued to evolve since 1929.
After the establishment of coronary angiography as a diagnostic tool, the limitation of exercise-induced ST-segment depression as a diagnostic marker for obstructive CAD in patient populations with a low disease prevalence became apparent.
Introduction
Exercise testing is a cardiovascular stress test using treadmill bicycle exercise with ECG and blood pressure monitoring. Pharmacologic stress testing, established after exercise testing, is a diagnostic procedure in which cardiovascular stress induced by pharmacologic agents is demonstrated in patients with decreased functional capacity or in patients who cannot exercise. Pharmacologic stress testing is used in combination with imaging modalities such as radionuclide imaging and echocardiography.
Exercise stress testing, which is now widely available at a relatively low cost, is currently used most frequently to estimate prognosis and determine functional capacity, to assess the probability and extent of coronary disease, and to assess the effects of therapy. Ancillary techniques, such as metabolic gas analysis, radionuclide imaging, and echocardiography, can provide further information that may be needed in selected patients, such as those with moderate or prior risk.
Exercise physiology
The initiation of dynamic exercise results in increases in the ventricular heart rate, stroke volume, and cardiac output due to vagal withdrawal and sympathetic stimulation. Also, alveolar ventilation and venous return increase as a result of sympathetic vasoconstriction. The overall hemodynamic response depends on the amount of muscle mass involved, exercise efficiency, conditioning, and exercise intensity.
In the initial phases of exercise in the upright position, cardiac output is increased by an augmentation in stroke volume mediated through the use of the Frank-Starling mechanism and heart rate. The increase in cardiac output in the later phases of exercise is due primarily to an increase in ventricular rate.
During strenuous exertion, sympathetic discharge is maximal and parasympathetic stimulation is withdrawn, resulting in autoregulation with generalized vasoconstriction, except in the vital organs (cerebral and coronary circulations).
Venous and arterial norepinephrine release from sympathetic postganglionic nerve endings is increased, and epinephrine levels are increased at peak exertion, resulting in an increase in ventricular contractility. As exercise progresses, skeletal muscle blood flow increases; oxygen extraction increases as much as 3-fold; peripheral resistance decreases; and systolic blood pressure (SBP), mean arterial pressure, and pulse pressure usually increase. Diastolic blood pressure (DBP) remains unchanged or may increase or decrease by approximately 10 mm Hg. The pulmonary vascular bed can accommodate as much as a 6-fold increase in cardiac output, with only modest increases in pulmonary arterial pressure, pulmonary capillary wedge pressure, and right atrial pressure; this is not a limiting determinant of peak exercise capacity in healthy subjects.
The maximum heart rate and cardiac output are decreased in older individuals, related in part to decreased beta-adrenergic responsiveness. Maximum heart rate can be calculated by subtracting the patient's age (y) from 220 (has a standard deviation of 10-12 beats per minute [bpm]). The age-predicted maximum heart rate is a useful measurement for safety reasons and as an estimate of the adequacy of the stress to evoke inducible ischemia. A patient who reaches 80% of the age-predicted maximum is considered to have a good test result, and an age-predicted maximum of 90% or better is considered excellent.
In the postexercise phase, hemodynamics return to baseline within minutes of discontinuing exercise. The return of vagal stimulation is an important cardiac deceleration mechanism after exercise and is more pronounced in well-trained athletes but blunted in patients with chronic congestive heart failure. Intense physical work or important cardiorespiratory impairment may interfere with achievement of a steady state, and an oxygen deficit occurs during exercise. The oxygen debt is the total oxygen uptake in excess of the resting oxygen uptake during the recovery period.
Thursday 26 June 2008
Cor pulmonale
Cor pulmonale is defined as an alteration in the structure and function of the right ventricle caused by a primary disorder of the respiratory system. Pulmonary hypertension is the common link between lung dysfunction and the heart in cor pulmonale. Right-sided ventricular disease caused by a primary abnormality of the left side of the heart or congenital heart disease is not considered cor pulmonale, but cor pulmonale can develop secondary to a wide variety of cardiopulmonary disease processes. Although cor pulmonale commonly has a chronic and slowly progressive course, acute onset or worsening cor pulmonale with life-threatening complications can occur.
Pathophysiology: Several different pathophysiologic mechanisms can lead to pulmonary hypertension and, subsequently, to cor pulmonale. These pathogenetic mechanisms include (1) pulmonary vasoconstriction due to alveolar hypoxia or blood acidemia; (2) anatomic compromise of the pulmonary vascular bed secondary to lung disorders, eg, emphysema, pulmonary thromboembolism, interstitial lung disease; (3) increased blood viscosity secondary to blood disorders, eg, polycythemia vera, sickle cell disease, macroglobulinemia; and (4) idiopathic primary pulmonary hypertension. The result is increased pulmonary arterial pressure.
The right ventricle (RV) is a thin-walled chamber that is more a volume pump than a pressure pump. It adapts better to changing preloads than afterloads. With an increase in afterload, the RV increases systolic pressure to keep the gradient. At a point, further increase in the degree of pulmonary arterial pressure brings significant RV dilation, an increase in RV end-diastolic pressure, and circulatory collapse. A decrease in RV output with a decrease in diastolic left ventricle (LV) volume results in decreased LV output. Since the right coronary artery, which supplies the RV free wall, originates from the aorta, decreased LV output diminishes blood pressure in the aorta and decreases right coronary blood flow. This is a vicious cycle between decreases in LV and RV output.
Right ventricular overload is associated with septal displacement toward the left ventricle. Septal displacement, which is seen in echocardiography, can be another factor that decreases LV volume and output in the setting of cor pulmonale and right ventricular enlargement. Several pulmonary diseases cause cor pulmonale, which may involve interstitial and alveolar tissues with a secondary effect on pulmonary vasculature or may primarily involve pulmonary vasculature. Chronic obstructive pulmonary disease (COPD) is the most common cause of cor pulmonale in the United States.
Cor pulmonale usually presents chronically, but 2 main conditions can cause acute cor pulmonale: massive pulmonary embolism (more common) and acute respiratory distress syndrome (ARDS). The underlying pathophysiology in massive pulmonary embolism causing cor pulmonale is the sudden increase in pulmonary resistance. In ARDS, 2 factors cause RV overload: the pathologic features of the syndrome itself and mechanical ventilation. Mechanical ventilation, especially higher tidal volume, requires a higher transpulmonary pressure. In chronic cor pulmonale, right ventricular hypertrophy (RVH) generally predominates. In acute cor pulmonale, right ventricular dilatation mainly occurs.
Frequency:
In the US: Cor pulmonale is estimated to account for 6-7% of all types of adult heart disease in the United States, with chronic obstructive pulmonary disease (COPD) due to chronic bronchitis or emphysema the causative factor in more than 50% of cases. Although the prevalence of COPD in the United States is about 15 million, the exact prevalence of cor pulmonale is difficult to determine because it does not occur in all cases of COPD and the physical examination and routine tests are relatively insensitive for the detection of pulmonary hypertension. In contrast, acute cor pulmonale usually is secondary to massive pulmonary embolism. Acute massive pulmonary thromboembolism is the most common cause of acute life-threatening cor pulmonale in adults. In the United States, 50,000 deaths are estimated to occur per year from pulmonary emboli and about half occur within the first hour due to acute right heart failure.
Internationally: Incidence of cor pulmonale varies among different countries depending on the prevalence of cigarette smoking, air pollution, and other risk factors for various lung diseases.
Mortality/Morbidity: Development of cor pulmonale as a result of a primary pulmonary disease usually heralds a poorer prognosis. For example, patients with COPD who develop cor pulmonale have a 30% chance of surviving 5 years. However, whether cor pulmonale carries an independent prognostic value or it is simply reflecting the severity of underlying COPD or other pulmonary disease is not clear. Prognosis in the acute setting due to massive pulmonary embolism or ARDS has not been shown to be dependent on presence or absence of cor pulmonale.
Pathophysiology: Several different pathophysiologic mechanisms can lead to pulmonary hypertension and, subsequently, to cor pulmonale. These pathogenetic mechanisms include (1) pulmonary vasoconstriction due to alveolar hypoxia or blood acidemia; (2) anatomic compromise of the pulmonary vascular bed secondary to lung disorders, eg, emphysema, pulmonary thromboembolism, interstitial lung disease; (3) increased blood viscosity secondary to blood disorders, eg, polycythemia vera, sickle cell disease, macroglobulinemia; and (4) idiopathic primary pulmonary hypertension. The result is increased pulmonary arterial pressure.
The right ventricle (RV) is a thin-walled chamber that is more a volume pump than a pressure pump. It adapts better to changing preloads than afterloads. With an increase in afterload, the RV increases systolic pressure to keep the gradient. At a point, further increase in the degree of pulmonary arterial pressure brings significant RV dilation, an increase in RV end-diastolic pressure, and circulatory collapse. A decrease in RV output with a decrease in diastolic left ventricle (LV) volume results in decreased LV output. Since the right coronary artery, which supplies the RV free wall, originates from the aorta, decreased LV output diminishes blood pressure in the aorta and decreases right coronary blood flow. This is a vicious cycle between decreases in LV and RV output.
Right ventricular overload is associated with septal displacement toward the left ventricle. Septal displacement, which is seen in echocardiography, can be another factor that decreases LV volume and output in the setting of cor pulmonale and right ventricular enlargement. Several pulmonary diseases cause cor pulmonale, which may involve interstitial and alveolar tissues with a secondary effect on pulmonary vasculature or may primarily involve pulmonary vasculature. Chronic obstructive pulmonary disease (COPD) is the most common cause of cor pulmonale in the United States.
Cor pulmonale usually presents chronically, but 2 main conditions can cause acute cor pulmonale: massive pulmonary embolism (more common) and acute respiratory distress syndrome (ARDS). The underlying pathophysiology in massive pulmonary embolism causing cor pulmonale is the sudden increase in pulmonary resistance. In ARDS, 2 factors cause RV overload: the pathologic features of the syndrome itself and mechanical ventilation. Mechanical ventilation, especially higher tidal volume, requires a higher transpulmonary pressure. In chronic cor pulmonale, right ventricular hypertrophy (RVH) generally predominates. In acute cor pulmonale, right ventricular dilatation mainly occurs.
Frequency:
In the US: Cor pulmonale is estimated to account for 6-7% of all types of adult heart disease in the United States, with chronic obstructive pulmonary disease (COPD) due to chronic bronchitis or emphysema the causative factor in more than 50% of cases. Although the prevalence of COPD in the United States is about 15 million, the exact prevalence of cor pulmonale is difficult to determine because it does not occur in all cases of COPD and the physical examination and routine tests are relatively insensitive for the detection of pulmonary hypertension. In contrast, acute cor pulmonale usually is secondary to massive pulmonary embolism. Acute massive pulmonary thromboembolism is the most common cause of acute life-threatening cor pulmonale in adults. In the United States, 50,000 deaths are estimated to occur per year from pulmonary emboli and about half occur within the first hour due to acute right heart failure.
Internationally: Incidence of cor pulmonale varies among different countries depending on the prevalence of cigarette smoking, air pollution, and other risk factors for various lung diseases.
Mortality/Morbidity: Development of cor pulmonale as a result of a primary pulmonary disease usually heralds a poorer prognosis. For example, patients with COPD who develop cor pulmonale have a 30% chance of surviving 5 years. However, whether cor pulmonale carries an independent prognostic value or it is simply reflecting the severity of underlying COPD or other pulmonary disease is not clear. Prognosis in the acute setting due to massive pulmonary embolism or ARDS has not been shown to be dependent on presence or absence of cor pulmonale.
Wednesday 25 June 2008
Brugada Syndrome
Background
Brugada syndrome is a disorder characterized by coved or saddle-shaped ST-segment elevation in leads V1 through V3 on ECG. It is associated with complete or incomplete right bundle-branch block and T-wave inversion. In its initial description, the heart was reported to be structurally normal, but this has recently been challenged (Frustaci, 2005). Moreover, subtle structural abnormalities in the right ventricular outflow tract can also be observed. The ECG abnormality may not be evident until it is unmasked by infusion of flecainide or procainamide, or is augmented by a beta-blocker.
Patients with Brugada syndrome are prone to develop ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden cardiac death (Martini, 1989; Brugada, 1992; Brugada, 2001). Brugada syndrome is genetically determined and has an autosomal dominant pattern of transmission in about 50% of familial cases. About 5% of survivors of cardiac arrest have no clinically identified cardiac abnormality; about half of these cases are thought to be due to Brugada syndrome (Alings, 1999).
Pathophysiology
Dysfunction in cardiac ion channels underlies the clinical manifestations of Brugada syndrome (cardiac channelopathy). In 10-30% of patients and families, mutations in the gene SCN5A, encoding the cardiac voltage-gated sodium channel Nav1.5, have been reported. Another locus has also been reported on chromosome 3. Most SCN5A mutations lead to loss of function of the Nav1.5 channel by reducing the sodium current (INa) available during the phases 0 (upstroke) and 1 (early repolarization) of the cardiac action potential. Gain-of-function SCN5A mutations may also cause long QT syndrome type 3.
Repolarization disorder hypothesis
ECG alterations in Brugada syndrome have been proposed to be due to an imbalance between the depolarizing and repolarizing currents during phase 1 of the action potential, most particularly in cells expressing a large, transient outward Ito current, such as the epicardial cells of the right ventricle free wall. In patients with loss-of-function SCN5A mutations that result in less INa during phase 1, the large Ito current may prematurely repolarize the membrane and produce a loss of the dome (phase 2) of the action potential (see Image 1).
When such premature shortening of the action potential heterogeneously occurs in the myocardium, it may generate phase 2 reentries that can cause ventricular tachycardia and ventricular fibrillation. The large transmural voltage gradients generated by the short action potentials in the right ventricular outflow epicardium are thought to be the basis of the ECG patterns of Brugada syndrome. These specific alterations in cardiac electrical activity, which mainly affect the right ventricle, manifest at ST-segment elevation in precordial leads V1 through V3, with a QRS morphology resembling that of a right bundle-branch block (RBBB). Such a pattern may also be due to a J point elevation. This pattern is called coved-type when ST elevation is the most prominent feature, and it is called saddleback-type when J point elevation occurs without ST elevation (see Image 2).
Depolarization disorder model
An alternative hypothesis for the ECG alterations is based on conduction delay in the right ventricular outflow tract compared with the right ventricle free wall. The mechanisms underlying the Brugada syndrome ECG pattern are reviewed by Meregalli (Meregalli, 2005).
The ECG pattern in Brugada syndrome may only be intermittent. The ECG alterations may fluctuate with changes in autonomic balance or body temperature. The abnormality may only be apparent during administration of drugs that block the sodium channel (eg, flecainide, procainamide, ajmaline). The ECG abnormality may disappear with infusion of isoprenaline or with exercise, and it may increase with beta-blockers. These effects are explained by a reduced sodium current in the etiology of Brugada syndrome.
Frequency
United States
Because of its recent identification, the incidence of the Brugada syndrome is not well established. It may cause 4-10 sudden deaths per 10,000 population per year.
International
In Asia (eg, the Philippines, Thailand, Japan), Brugada syndrome seems to be the most common cause of natural death in men younger than 50 years. It is known as Lai Tai (Thailand), Bangungut (Philippines), and Pokkuri (Japan). In Northeast Thailand, the mortality rate from Lai Tai is approximately 30 per 100,000 population per year (Nademanee, 1997).
Mortality/Morbidity
Brugada syndrome may lead to polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and cause sudden cardiac death.
Prolonged syncope and aborted cardiac arrest may cause nightmares, seizures, other neurologic deficits, or brain damage.
Race
Brugada syndrome is most common in people from Asia. The reason for this observation is not yet fully understood but may be due to an Asian-specific sequence in the promoter region of SCN5A (Bezzina, 2005).
Sex
Brugada syndrome is 8-10 times more prevalent in men than in women, although the probability of having a mutated gene does not differ by sex. The penetrance of the mutation appears to be much higher in men than in women.
Age
Brugada syndrome most commonly affects otherwise healthy men aged 30-50 years, but affected patients aged 0-84 years have been reported. The mean age of patients who die suddenly is 41 years (Antzelevitch, 2005).
Read more HERE
Brugada syndrome is a disorder characterized by coved or saddle-shaped ST-segment elevation in leads V1 through V3 on ECG. It is associated with complete or incomplete right bundle-branch block and T-wave inversion. In its initial description, the heart was reported to be structurally normal, but this has recently been challenged (Frustaci, 2005). Moreover, subtle structural abnormalities in the right ventricular outflow tract can also be observed. The ECG abnormality may not be evident until it is unmasked by infusion of flecainide or procainamide, or is augmented by a beta-blocker.
Patients with Brugada syndrome are prone to develop ventricular tachyarrhythmias, which may lead to syncope, cardiac arrest, or sudden cardiac death (Martini, 1989; Brugada, 1992; Brugada, 2001). Brugada syndrome is genetically determined and has an autosomal dominant pattern of transmission in about 50% of familial cases. About 5% of survivors of cardiac arrest have no clinically identified cardiac abnormality; about half of these cases are thought to be due to Brugada syndrome (Alings, 1999).
Pathophysiology
Dysfunction in cardiac ion channels underlies the clinical manifestations of Brugada syndrome (cardiac channelopathy). In 10-30% of patients and families, mutations in the gene SCN5A, encoding the cardiac voltage-gated sodium channel Nav1.5, have been reported. Another locus has also been reported on chromosome 3. Most SCN5A mutations lead to loss of function of the Nav1.5 channel by reducing the sodium current (INa) available during the phases 0 (upstroke) and 1 (early repolarization) of the cardiac action potential. Gain-of-function SCN5A mutations may also cause long QT syndrome type 3.
Repolarization disorder hypothesis
ECG alterations in Brugada syndrome have been proposed to be due to an imbalance between the depolarizing and repolarizing currents during phase 1 of the action potential, most particularly in cells expressing a large, transient outward Ito current, such as the epicardial cells of the right ventricle free wall. In patients with loss-of-function SCN5A mutations that result in less INa during phase 1, the large Ito current may prematurely repolarize the membrane and produce a loss of the dome (phase 2) of the action potential (see Image 1).
When such premature shortening of the action potential heterogeneously occurs in the myocardium, it may generate phase 2 reentries that can cause ventricular tachycardia and ventricular fibrillation. The large transmural voltage gradients generated by the short action potentials in the right ventricular outflow epicardium are thought to be the basis of the ECG patterns of Brugada syndrome. These specific alterations in cardiac electrical activity, which mainly affect the right ventricle, manifest at ST-segment elevation in precordial leads V1 through V3, with a QRS morphology resembling that of a right bundle-branch block (RBBB). Such a pattern may also be due to a J point elevation. This pattern is called coved-type when ST elevation is the most prominent feature, and it is called saddleback-type when J point elevation occurs without ST elevation (see Image 2).
Depolarization disorder model
An alternative hypothesis for the ECG alterations is based on conduction delay in the right ventricular outflow tract compared with the right ventricle free wall. The mechanisms underlying the Brugada syndrome ECG pattern are reviewed by Meregalli (Meregalli, 2005).
The ECG pattern in Brugada syndrome may only be intermittent. The ECG alterations may fluctuate with changes in autonomic balance or body temperature. The abnormality may only be apparent during administration of drugs that block the sodium channel (eg, flecainide, procainamide, ajmaline). The ECG abnormality may disappear with infusion of isoprenaline or with exercise, and it may increase with beta-blockers. These effects are explained by a reduced sodium current in the etiology of Brugada syndrome.
Frequency
United States
Because of its recent identification, the incidence of the Brugada syndrome is not well established. It may cause 4-10 sudden deaths per 10,000 population per year.
International
In Asia (eg, the Philippines, Thailand, Japan), Brugada syndrome seems to be the most common cause of natural death in men younger than 50 years. It is known as Lai Tai (Thailand), Bangungut (Philippines), and Pokkuri (Japan). In Northeast Thailand, the mortality rate from Lai Tai is approximately 30 per 100,000 population per year (Nademanee, 1997).
Mortality/Morbidity
Brugada syndrome may lead to polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and cause sudden cardiac death.
Prolonged syncope and aborted cardiac arrest may cause nightmares, seizures, other neurologic deficits, or brain damage.
Race
Brugada syndrome is most common in people from Asia. The reason for this observation is not yet fully understood but may be due to an Asian-specific sequence in the promoter region of SCN5A (Bezzina, 2005).
Sex
Brugada syndrome is 8-10 times more prevalent in men than in women, although the probability of having a mutated gene does not differ by sex. The penetrance of the mutation appears to be much higher in men than in women.
Age
Brugada syndrome most commonly affects otherwise healthy men aged 30-50 years, but affected patients aged 0-84 years have been reported. The mean age of patients who die suddenly is 41 years (Antzelevitch, 2005).
Read more HERE
Tuesday 24 June 2008
Varicose Veins and Spider Veins
Varicose veins and telangiectasia (spider veins) are the visible surface manifestations of an underlying venous insufficiency syndrome. Venous insufficiency syndromes allow venous blood to escape from a normal flow path and flow in a retrograde direction into an already congested leg.
Mild forms of venous insufficiency are merely uncomfortable, annoying, or cosmetically disfiguring, but severe venous disease can produce serious systemic consequences and can lead to loss of life or limb.
Most patients with venous insufficiency have subjective symptoms that may include pain, soreness, burning, aching, throbbing, cramping, muscle fatigue, and restless legs. Over time, chronic venous insufficiency leads to cutaneous and soft tissue breakdown that can be debilitating.
Chronic venous insufficiency eventually produces chronic skin and soft tissue changes that begin with mild swelling and then progress to include discoloration, inflammatory dermatitis, recurrent or chronic cellulitis, cutaneous infarction, ulceration, and even malignant degeneration.
Chronic nonhealing leg ulcers, bleeding from varicose veins, and recurrent phlebitis are serious problems that are caused by venous insufficiency and can be relieved by the correction of venous insufficiency.
Pathophysiology
Varicose veins and spider veins are normal veins that have dilated under the influence of increased venous pressure.
In healthy veins, one-way valves direct the flow of venous blood upward and inward. Blood is collected in superficial venous capillaries, flows into larger superficial veins, and eventually passes through valves into the deep veins and then centrally to the heart and lungs. Superficial veins are suprafascial, while deep veins are within the muscle fascia. Perforating veins allow blood to pass from the superficial veins into the deep system.
Within muscle compartments, muscular contraction compresses deep veins and causes a pumping action that can produce transient deep venous pressures as high as 5 atmospheres. Deep veins can withstand this pressure because of their construction and because their confining fascia prevents them from becoming excessively distended. In contrast to deep veins, the venous pressure in superficial veins normally is very low. Exposure to high pressures causes superficial veins of any size to become dilated and tortuous.
Perfectly normal veins dilate and become tortuous in response to continued high pressure, as is observed in patients with dialysis shunts or with spontaneous arteriovenous malformations. In a subset of patients with hereditary vein wall weakness, even normal venous pressures produce varicose changes and venous insufficiency.
Elevated venous pressure most often is the result of venous insufficiency due to valve incompetence in the deep or superficial veins. Varicose veins are the undesirable pathways by which venous blood refluxes back into the congested extremity. Ablation of the varicose pathways invariably improves overall venous circulation.
Chronically increased venous pressure can also be caused by outflow obstruction, either from intravascular thrombosis or from extrinsic compression. In patients with outflow obstruction, varicosities must not be ablated because they are an important bypass pathway allowing blood to flow around the obstruction. Specific diagnostic tests can distinguish between patients who will benefit from ablation of dilated superficial veins and those who will be harmed by the same procedure.
Deep vein thrombosis initially produces an obstruction to outflow, but in most cases the thrombosed vessel eventually recanalizes and becomes a valveless channel delivering high pressures from above downward.
Superficial venous valve failure may result from direct trauma or from thrombotic valve injury, but most commonly is simply due to the effects of high pressure within the superficial venous system. When exposed to high pressure for a long enough period, superficial veins dilate so much that their delicate valve leaflets no longer meet.
In the most common scenario, a single venous valve fails and creates a high-pressure leak between the deep and superficial systems. High pressure within the superficial system causes local dilatation, which leads to sequential failure (through over-stretching) of other nearby valves in the superficial veins. After a series of valves have failed, the involved veins are no longer capable of directing blood upward and inward. Without functioning valves, venous blood flows in the direction of the pressure gradient: outward and downward into an already congested leg.
As increasing numbers of valves fail under the strain, high pressure is communicated into a widening network of dilated superficial veins in a recruitment phenomenon. Over time, large numbers of incompetent superficial veins acquire the typical dilated and tortuous appearance of varicosities.
Varicose veins of pregnancy most often are caused by hormonal changes that render the vein wall and the valves themselves more pliable. The sudden appearance of new dilated varicosities during pregnancy still warrants a full evaluation because of the possibility that these may be new bypass pathways related to acute deep vein thrombosis.
The sequelae of venous insufficiency are related to the venous pressure and to the volume of venous blood that is carried in a retrograde direction through incompetent veins. Unfortunately, the presence and size of visible varicosities are not reliable indicators of the volume or pressure of venous reflux. A vein that is confined within fascial planes or is buried beneath subcutaneous tissue can carry massive amounts of high-pressure reflux without being visible at all. Conversely, even a small increase in pressure can eventually produce massive dilatation of an otherwise normal superficial vein that carries very little flow.
Frequency
United States
The incidence and prevalence of venous insufficiency disease depend on the age and sex of the population. Varicosities were observed in 72% of women aged 60-69 years but in only 1% of men aged 20-29 years in the Tecumseh community health study.
International
The prevalence of venous disease is higher in Westernized and industrialized countries, most likely due to alterations in lifestyle and activity.
Mortality/Morbidity
Death can occur because of bleeding from friable varicose veins, but the mortality associated with varicose veins is almost entirely due to the association of this condition with venous thromboembolism. When treating a patient with varicose veins, the possibility of associated deep venous thrombosis must always be considered because the mortality rate of unrecognized and untreated thromboembolism is 30-60%.
Patients with varicose veins are at increased risk of deep vein thrombosis because venous stasis and injury often cause superficial phlebitis that can pass through perforating vessels to involve the deep venous system.
Varicose veins may arise after an unrecognized episode of deep vein thrombosis that causes damage to venous valves. Such patients have some underlying risk factor for thromboembolism and are at especially high risk for recurrence.
Varicose veins may sometimes serve as an important pathway for venous return in a patient with acute blockage of the deep venous system from any cause. This most often occurs after an episode of deep vein thrombosis, but it may also be a response to tumor growth or to impaired portal flow through a cirrhotic liver.
Sex
Because of hormonal factors, varicosities and telangiectasia are more common in women than in men at any age.
Age
Most varicose and spider veins in adults have their genesis in childhood. Serial examinations of children aged 10-12 years and again 4 and 8 years later showed that symptoms are experienced (and venous test results are abnormal) before any abnormal veins are visible at the surface of the skin.
When abnormal veins do become visible, reticular veins usually appear first and are followed after several years by incompetent perforators. Smaller telangiectatic webs and large varicose veins usually become visible only in adulthood, many years after the true onset of disease.
Although varicosities continue to worsen and to recruit new areas of involvement throughout life, only a small number of new cases appear after the childbearing years.
Read more HERE
Mild forms of venous insufficiency are merely uncomfortable, annoying, or cosmetically disfiguring, but severe venous disease can produce serious systemic consequences and can lead to loss of life or limb.
Most patients with venous insufficiency have subjective symptoms that may include pain, soreness, burning, aching, throbbing, cramping, muscle fatigue, and restless legs. Over time, chronic venous insufficiency leads to cutaneous and soft tissue breakdown that can be debilitating.
Chronic venous insufficiency eventually produces chronic skin and soft tissue changes that begin with mild swelling and then progress to include discoloration, inflammatory dermatitis, recurrent or chronic cellulitis, cutaneous infarction, ulceration, and even malignant degeneration.
Chronic nonhealing leg ulcers, bleeding from varicose veins, and recurrent phlebitis are serious problems that are caused by venous insufficiency and can be relieved by the correction of venous insufficiency.
Pathophysiology
Varicose veins and spider veins are normal veins that have dilated under the influence of increased venous pressure.
In healthy veins, one-way valves direct the flow of venous blood upward and inward. Blood is collected in superficial venous capillaries, flows into larger superficial veins, and eventually passes through valves into the deep veins and then centrally to the heart and lungs. Superficial veins are suprafascial, while deep veins are within the muscle fascia. Perforating veins allow blood to pass from the superficial veins into the deep system.
Within muscle compartments, muscular contraction compresses deep veins and causes a pumping action that can produce transient deep venous pressures as high as 5 atmospheres. Deep veins can withstand this pressure because of their construction and because their confining fascia prevents them from becoming excessively distended. In contrast to deep veins, the venous pressure in superficial veins normally is very low. Exposure to high pressures causes superficial veins of any size to become dilated and tortuous.
Perfectly normal veins dilate and become tortuous in response to continued high pressure, as is observed in patients with dialysis shunts or with spontaneous arteriovenous malformations. In a subset of patients with hereditary vein wall weakness, even normal venous pressures produce varicose changes and venous insufficiency.
Elevated venous pressure most often is the result of venous insufficiency due to valve incompetence in the deep or superficial veins. Varicose veins are the undesirable pathways by which venous blood refluxes back into the congested extremity. Ablation of the varicose pathways invariably improves overall venous circulation.
Chronically increased venous pressure can also be caused by outflow obstruction, either from intravascular thrombosis or from extrinsic compression. In patients with outflow obstruction, varicosities must not be ablated because they are an important bypass pathway allowing blood to flow around the obstruction. Specific diagnostic tests can distinguish between patients who will benefit from ablation of dilated superficial veins and those who will be harmed by the same procedure.
Deep vein thrombosis initially produces an obstruction to outflow, but in most cases the thrombosed vessel eventually recanalizes and becomes a valveless channel delivering high pressures from above downward.
Superficial venous valve failure may result from direct trauma or from thrombotic valve injury, but most commonly is simply due to the effects of high pressure within the superficial venous system. When exposed to high pressure for a long enough period, superficial veins dilate so much that their delicate valve leaflets no longer meet.
In the most common scenario, a single venous valve fails and creates a high-pressure leak between the deep and superficial systems. High pressure within the superficial system causes local dilatation, which leads to sequential failure (through over-stretching) of other nearby valves in the superficial veins. After a series of valves have failed, the involved veins are no longer capable of directing blood upward and inward. Without functioning valves, venous blood flows in the direction of the pressure gradient: outward and downward into an already congested leg.
As increasing numbers of valves fail under the strain, high pressure is communicated into a widening network of dilated superficial veins in a recruitment phenomenon. Over time, large numbers of incompetent superficial veins acquire the typical dilated and tortuous appearance of varicosities.
Varicose veins of pregnancy most often are caused by hormonal changes that render the vein wall and the valves themselves more pliable. The sudden appearance of new dilated varicosities during pregnancy still warrants a full evaluation because of the possibility that these may be new bypass pathways related to acute deep vein thrombosis.
The sequelae of venous insufficiency are related to the venous pressure and to the volume of venous blood that is carried in a retrograde direction through incompetent veins. Unfortunately, the presence and size of visible varicosities are not reliable indicators of the volume or pressure of venous reflux. A vein that is confined within fascial planes or is buried beneath subcutaneous tissue can carry massive amounts of high-pressure reflux without being visible at all. Conversely, even a small increase in pressure can eventually produce massive dilatation of an otherwise normal superficial vein that carries very little flow.
Frequency
United States
The incidence and prevalence of venous insufficiency disease depend on the age and sex of the population. Varicosities were observed in 72% of women aged 60-69 years but in only 1% of men aged 20-29 years in the Tecumseh community health study.
International
The prevalence of venous disease is higher in Westernized and industrialized countries, most likely due to alterations in lifestyle and activity.
Mortality/Morbidity
Death can occur because of bleeding from friable varicose veins, but the mortality associated with varicose veins is almost entirely due to the association of this condition with venous thromboembolism. When treating a patient with varicose veins, the possibility of associated deep venous thrombosis must always be considered because the mortality rate of unrecognized and untreated thromboembolism is 30-60%.
Patients with varicose veins are at increased risk of deep vein thrombosis because venous stasis and injury often cause superficial phlebitis that can pass through perforating vessels to involve the deep venous system.
Varicose veins may arise after an unrecognized episode of deep vein thrombosis that causes damage to venous valves. Such patients have some underlying risk factor for thromboembolism and are at especially high risk for recurrence.
Varicose veins may sometimes serve as an important pathway for venous return in a patient with acute blockage of the deep venous system from any cause. This most often occurs after an episode of deep vein thrombosis, but it may also be a response to tumor growth or to impaired portal flow through a cirrhotic liver.
Sex
Because of hormonal factors, varicosities and telangiectasia are more common in women than in men at any age.
Age
Most varicose and spider veins in adults have their genesis in childhood. Serial examinations of children aged 10-12 years and again 4 and 8 years later showed that symptoms are experienced (and venous test results are abnormal) before any abnormal veins are visible at the surface of the skin.
When abnormal veins do become visible, reticular veins usually appear first and are followed after several years by incompetent perforators. Smaller telangiectatic webs and large varicose veins usually become visible only in adulthood, many years after the true onset of disease.
Although varicosities continue to worsen and to recruit new areas of involvement throughout life, only a small number of new cases appear after the childbearing years.
Read more HERE
Monday 23 June 2008
Friday 20 June 2008
Acute Renal Failure
Background
Acute renal failure (ARF) or acute kidney injury (AKI), as it is now referred to in the literature, is defined as an abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum creatinine concentration or azotemia (a rise in blood urea nitrogen [BUN] concentration). However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production. A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim) that inhibit the kidney’s tubular secretion. A rise in the BUN level can occur without renal injury, such as in GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be taken before determining if a kidney injury is present.
Pathophysiology
AKI may occur in 3 clinical patterns, including the following: (1) as an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons; (2) in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage; and (3) with obstruction to the passage of urine. Therefore, in general terms, AKI may be classified as prerenal, intrinsic, and postrenal. While these classifications are useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories.
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in creatinine levels, and may have qualitative differences in urine solute concentrations and cellular content. The reason for this lack of a uniform clinical presentation is a reflection of the variable nature of the injury. Classifying AKI as oliguric or nonoliguric based on daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure. Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, is suggestive of bilateral obstruction or catastrophic injury to both kidneys. Stratification of renal failure along these lines helps in decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.
Prerenal AKIPrerenal AKI represents the most common form of kidney injury and often leads to intrinsic AKI if it is not promptly corrected. Volume loss from GI, renal, cutaneous (eg, burns), and internal or external hemorrhage can result in this syndrome. Prerenal AKI can also result from decreased renal perfusion in patients with heart failure or shock (eg, sepsis, anaphylaxis). Special classes of medications that can induce prerenal AKI in volume-depleted states are angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which are otherwise safely tolerated and beneficial in most patients with chronic kidney disease. Arteriolar vasoconstriction leading to prerenal AKI can occur in hypercalcemic states, with the use of radiocontrast agents, nonsteroidal anti-inflammatory drugs (NSAIDs), amphotereicin, calcineurin inhibitors, norepinephrine, and other pressor agents. The hepatorenal syndrome can also be considered a form of prerenal AKI because functional renal failure develops from diffuse vasoconstriction in vessels supplying the kidney.Intrinsic AKI
Structural injury in the kidney is the hallmark of intrinsic AKI, and the most common form is acute tubular injury (ATN), either ischemic or cytotoxic. Frank necrosis is not prominent in most human cases of ATN and tends to be patchy. Less obvious injury includes loss of brush borders, flattening of the epithelium, detachment of cells, formation of intratubular casts, and dilatation of the lumen. Although these changes are observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated. The distal nephron may also be subjected to obstruction by desquamated cells and cellular debris. In contrast to necrosis, the principal site of apoptotic cell death is the distal nephron. During the initial phase of ischemic injury, loss of integrity of the actin cytoskeleton leads to flattening of the epithelium, with loss of the brush border, loss of focal cell contacts, and subsequent disengagement of the cell from the underlying substratum.
Many endogenous growth factors that participate in the process of regeneration have not been identified; however, administration of growth factors exogenously has been shown to ameliorate and hasten recovery from AKI. Depletion of neutrophils and blockage of neutrophil adhesion reduce renal injury following ischemia, indicating that the inflammatory response is responsible, in part, for some features of ATN, especially in postischemic injury after transplant.
Intrarenal vasoconstriction is the dominant mechanism for the reduced glomerular filtration rate (GFR) in patients with ATN. The mediators of this vasoconstriction are unknown, but tubular injury seems to be an important concomitant finding. Urine backflow and intratubular obstruction (from sloughed cells and debris) are causes of reduced net ultrafiltration. The importance of this mechanism is highlighted by the improvement in renal function that follows relief of such intratubular obstruction. In addition, when obstruction is prolonged, intrarenal vasoconstriction is prominent in part due to the tubuloglomerular feedback mechanism, which is thought to be mediated by adenosine and activated when there is proximal tubular damage and the macula densa is presented with increased chloride load.
Apart from the increase in basal renal vascular tone, the stressed renal microvasculature is more sensitive to potentially vasoconstrictive drugs and otherwise-tolerated changes in systemic blood pressure. The vasculature of the injured kidney has an impaired vasodilatory response and loses its autoregulatory behavior. This latter phenomenon has important clinical relevance because the frequent reduction in systemic pressure during intermittent hemodialysis may provoke additional damage that can delay recovery from ATN. Often, injury results in atubular glomeruli, where the glomerular function is preserved, but the lack of tubular outflow precludes its function.A physiologic hallmark of ATN is a failure to maximally dilute or concentrate urine (isosthenuria). This defect is not responsive to pharmacologic doses of vasopressin. The injured kidney fails to generate and maintain a high medullary solute gradient because the accumulation of solute in the medulla depends on normal distal nephron function. Failure to excrete concentrated urine, even in the presence of oliguria, is a helpful diagnostic clue to distinguish prerenal from intrinsic renal disease, in which urine osmolality is less than 300 mOsm/kg. In prerenal azotemia, urine osmolality is typically more than 500 mOsm/kg. Glomerulonephritis can be a cause of AKI and usually falls into a class referred to as rapidly progressive glomerulonephritis (RPGN). The pathologic correlation of RPGN is the presence of glomerular crescents (glomerular injury) on biopsy; if more than 50% of glomeruli contain crescents, this usually results in a significant decline in renal function. Although comparatively rare, acute glomerulonephritides should be part of the diagnostic consideration in cases of AKI.Postrenal AKI
Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or urethra, results in obstructive uropathy or postrenal AKI.
If the site of obstruction is unilateral, then a rise in the serum creatinine level may not be apparent due to contralateral renal function. Although the serum creatinine level may remain low with unilateral obstruction, a significant loss of GFR occurs, and patients with partial obstruction may develop progressive loss of GFR if the obstruction is not relieved. Causes of obstruction include stone disease; stricture; and intraluminal, extraluminal, or intramural tumors.
Bilateral obstruction is usually a result of prostate enlargement or tumors in men and urologic or gynecologic tumors in women.
Patients who develop anuria typically have obstruction at the level of the bladder or downstream to it.
Frequency
United States
Approximately 1% of patients admitted to hospitals have AKI at the time of admission, and the estimated incidence rate of AKI is 2-5% during hospitalization. Approximately 95% of consultations with nephrologists are related to AKI. Feest and colleagues calculated in their report that the appropriate nephrologist referral rate is approximately 70 cases per million population.1
Mortality/Morbidity
The mortality rate estimates vary from 25-90%. The in-hospital mortality rate is 40-50%; in intensive care settings, the rate is 70-80%. Increments of 0.3 mg/dL in serum creatinine have important prognostic significance.
Race
No racial predilection is recognized.
Read more HERE
Acute renal failure (ARF) or acute kidney injury (AKI), as it is now referred to in the literature, is defined as an abrupt or rapid decline in renal filtration function. This condition is usually marked by a rise in serum creatinine concentration or azotemia (a rise in blood urea nitrogen [BUN] concentration). However, immediately after a kidney injury, BUN or creatinine levels may be normal, and the only sign of a kidney injury may be decreased urine production. A rise in the creatinine level can result from medications (eg, cimetidine, trimethoprim) that inhibit the kidney’s tubular secretion. A rise in the BUN level can occur without renal injury, such as in GI or mucosal bleeding, steroid use, or protein loading, so a careful inventory must be taken before determining if a kidney injury is present.
Pathophysiology
AKI may occur in 3 clinical patterns, including the following: (1) as an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons; (2) in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage; and (3) with obstruction to the passage of urine. Therefore, in general terms, AKI may be classified as prerenal, intrinsic, and postrenal. While these classifications are useful in establishing a differential diagnosis, many pathophysiologic features are shared among the different categories.
Patients who develop AKI can be oliguric or nonoliguric, have a rapid or slow rise in creatinine levels, and may have qualitative differences in urine solute concentrations and cellular content. The reason for this lack of a uniform clinical presentation is a reflection of the variable nature of the injury. Classifying AKI as oliguric or nonoliguric based on daily urine excretion has prognostic value. Oliguria is defined as a daily urine volume of less than 400 mL/d and has a worse prognosis, except in prerenal failure. Anuria is defined as a urine output of less than 100 mL/d and, if abrupt in onset, is suggestive of bilateral obstruction or catastrophic injury to both kidneys. Stratification of renal failure along these lines helps in decision-making (eg, timing of dialysis) and can be an important criterion for patient response to therapy.
Prerenal AKIPrerenal AKI represents the most common form of kidney injury and often leads to intrinsic AKI if it is not promptly corrected. Volume loss from GI, renal, cutaneous (eg, burns), and internal or external hemorrhage can result in this syndrome. Prerenal AKI can also result from decreased renal perfusion in patients with heart failure or shock (eg, sepsis, anaphylaxis). Special classes of medications that can induce prerenal AKI in volume-depleted states are angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which are otherwise safely tolerated and beneficial in most patients with chronic kidney disease. Arteriolar vasoconstriction leading to prerenal AKI can occur in hypercalcemic states, with the use of radiocontrast agents, nonsteroidal anti-inflammatory drugs (NSAIDs), amphotereicin, calcineurin inhibitors, norepinephrine, and other pressor agents. The hepatorenal syndrome can also be considered a form of prerenal AKI because functional renal failure develops from diffuse vasoconstriction in vessels supplying the kidney.Intrinsic AKI
Structural injury in the kidney is the hallmark of intrinsic AKI, and the most common form is acute tubular injury (ATN), either ischemic or cytotoxic. Frank necrosis is not prominent in most human cases of ATN and tends to be patchy. Less obvious injury includes loss of brush borders, flattening of the epithelium, detachment of cells, formation of intratubular casts, and dilatation of the lumen. Although these changes are observed predominantly in proximal tubules, injury to the distal nephron can also be demonstrated. The distal nephron may also be subjected to obstruction by desquamated cells and cellular debris. In contrast to necrosis, the principal site of apoptotic cell death is the distal nephron. During the initial phase of ischemic injury, loss of integrity of the actin cytoskeleton leads to flattening of the epithelium, with loss of the brush border, loss of focal cell contacts, and subsequent disengagement of the cell from the underlying substratum.
Many endogenous growth factors that participate in the process of regeneration have not been identified; however, administration of growth factors exogenously has been shown to ameliorate and hasten recovery from AKI. Depletion of neutrophils and blockage of neutrophil adhesion reduce renal injury following ischemia, indicating that the inflammatory response is responsible, in part, for some features of ATN, especially in postischemic injury after transplant.
Intrarenal vasoconstriction is the dominant mechanism for the reduced glomerular filtration rate (GFR) in patients with ATN. The mediators of this vasoconstriction are unknown, but tubular injury seems to be an important concomitant finding. Urine backflow and intratubular obstruction (from sloughed cells and debris) are causes of reduced net ultrafiltration. The importance of this mechanism is highlighted by the improvement in renal function that follows relief of such intratubular obstruction. In addition, when obstruction is prolonged, intrarenal vasoconstriction is prominent in part due to the tubuloglomerular feedback mechanism, which is thought to be mediated by adenosine and activated when there is proximal tubular damage and the macula densa is presented with increased chloride load.
Apart from the increase in basal renal vascular tone, the stressed renal microvasculature is more sensitive to potentially vasoconstrictive drugs and otherwise-tolerated changes in systemic blood pressure. The vasculature of the injured kidney has an impaired vasodilatory response and loses its autoregulatory behavior. This latter phenomenon has important clinical relevance because the frequent reduction in systemic pressure during intermittent hemodialysis may provoke additional damage that can delay recovery from ATN. Often, injury results in atubular glomeruli, where the glomerular function is preserved, but the lack of tubular outflow precludes its function.A physiologic hallmark of ATN is a failure to maximally dilute or concentrate urine (isosthenuria). This defect is not responsive to pharmacologic doses of vasopressin. The injured kidney fails to generate and maintain a high medullary solute gradient because the accumulation of solute in the medulla depends on normal distal nephron function. Failure to excrete concentrated urine, even in the presence of oliguria, is a helpful diagnostic clue to distinguish prerenal from intrinsic renal disease, in which urine osmolality is less than 300 mOsm/kg. In prerenal azotemia, urine osmolality is typically more than 500 mOsm/kg. Glomerulonephritis can be a cause of AKI and usually falls into a class referred to as rapidly progressive glomerulonephritis (RPGN). The pathologic correlation of RPGN is the presence of glomerular crescents (glomerular injury) on biopsy; if more than 50% of glomeruli contain crescents, this usually results in a significant decline in renal function. Although comparatively rare, acute glomerulonephritides should be part of the diagnostic consideration in cases of AKI.Postrenal AKI
Mechanical obstruction of the urinary collecting system, including the renal pelvis, ureters, bladder, or urethra, results in obstructive uropathy or postrenal AKI.
If the site of obstruction is unilateral, then a rise in the serum creatinine level may not be apparent due to contralateral renal function. Although the serum creatinine level may remain low with unilateral obstruction, a significant loss of GFR occurs, and patients with partial obstruction may develop progressive loss of GFR if the obstruction is not relieved. Causes of obstruction include stone disease; stricture; and intraluminal, extraluminal, or intramural tumors.
Bilateral obstruction is usually a result of prostate enlargement or tumors in men and urologic or gynecologic tumors in women.
Patients who develop anuria typically have obstruction at the level of the bladder or downstream to it.
Frequency
United States
Approximately 1% of patients admitted to hospitals have AKI at the time of admission, and the estimated incidence rate of AKI is 2-5% during hospitalization. Approximately 95% of consultations with nephrologists are related to AKI. Feest and colleagues calculated in their report that the appropriate nephrologist referral rate is approximately 70 cases per million population.1
Mortality/Morbidity
The mortality rate estimates vary from 25-90%. The in-hospital mortality rate is 40-50%; in intensive care settings, the rate is 70-80%. Increments of 0.3 mg/dL in serum creatinine have important prognostic significance.
Race
No racial predilection is recognized.
Read more HERE
Thursday 19 June 2008
Syndrome of Inappropriate Secretion of Antidiuretic Hormone
Background
Water balance is an important regulatory function involving the hypothalamus and the kidneys (among other organs). Various hormones are also involved, of which the antidiuretic hormone (ADH) arginine vasopressin is most important.
The syndrome of inappropriate secretion of ADH (SIADH) is characterized by the nonphysiologic release of ADH, resulting in impaired water excretion with normal sodium excretion.
SIADH was first described by Schwartz and associates in 2 patients with bronchogenic carcinoma and was later further characterized by Bartter and Schwartz.
Pathophysiology
ADH is a polypeptide synthesized in the supraoptic and paraventricular nuclei in the hypothalamus and is released in response to a number of stimuli. ADH is rapidly metabolized in the liver and kidneys and has a half-life of 15-20 minutes.
In the kidneys, ADH acts on the principal cells of the cortical and medullary collecting tubules to increase water permeability. Other renal actions include local production of prostaglandins in a variety of renal cells, including the glomerulus and the thick ascending limb of the loop of Henle. Elsewhere, ADH causes vasoconstriction in a number of vascular beds and releases factor VIII and von Willebrand factor from vascular endothelium.
Three known receptors bind ADH at the cell membrane: V1a, V1b (also known as V3), and V2. The vasopressin (AVP, ADH) receptor subtypes belong to the G protein–coupled receptor superfamily. The V1a and V1b receptors signal by activation of phospholipase C and elevation in intracellular calcium, which, in turn, stimulates protein kinase C.
V1a subtype is ubiquitous and found on cells, such as vascular smooth muscle cells, hepatocytes, platelets, brain cells, and uterus cells. V1b receptors are found predominantly in the anterior pituitary.
V2 receptors are coupled to adenylate cyclase, causing a rise in intracellular cyclic adenosine monophosphate (cAMP), which serves as the second messenger. V2 receptors are found predominantly in the principal cells of the renal collecting duct, where they mediate antidiuretic response. V2 receptors are also found in endothelial cells and induce the secretion of von Willebrand factor.
ADH activates the V2 receptor on the basolateral membrane of the principal cells of the renal collecting duct. This activates cyclic adenosine monophosphate through heterotrimeric G proteins, which results in insertion of aquaporin-2 water channels in the luminal membrane, thus making it more permeable to water.
The major stimuli to ADH are hyperosmolality and effective circulating volume depletion. Normally, ADH secretion ceases when plasma osmolality falls below 275 mOsm/kg. This fall causes increased water excretion, which leads to a dilute urine with an osmolality of 40-100 mOsm/kg. In addition to the hypothalamic osmoreceptors, hypothalamic neurons secreting ADH also receive input from baroreceptors in the great vessels and the atria. This results in nonosmotic release of ADH. Other stimuli for ADH secretion include pain and nausea.
In general, the plasma sodium concentration is the primary osmotic determinant of ADH release. However, in persons with SIADH, a nonphysiologic secretion of ADH results in enhanced water reabsorption, leading to dilutional hyponatremia. Sodium excretion is intact, and the amount of sodium excreted in the urine varies with diet. Ingestion of water is an essential prerequisite to the development of dilutional hyponatremia; regardless of cause, hyponatremia does not occur if water is restricted.
The continued presence of ADH with water intake causes retention of ingested water. While a large fraction of this water is intracellular, the extracellular fraction causes volume expansion. Volume receptors are activated and peptides (eg, atrial natriuretic peptide) are secreted, which causes natriuresis with some degree of accompanying kaliuresis and diuresis. Thus, these patients are euvolemic or are slightly volume-expanded.
If water and sodium intake remain constant, a steady state is reached and sodium excretion equals sodium intake. Experimental evidence indicates that several days after ADH-induced water retention, escape from its effect occurs. This results in the establishment of a water balance and a newer, stable (although lower) sodium concentration. This is thought to be mediated via pressure-induced natriuresis and diuresis. Other authorities attribute this escape phenomenon to a decrease in the aquaporin-2 channel expression in the renal collecting duct.
In addition to the inappropriate ADH secretion, persons with this syndrome also may have an inappropriate thirst sensation, which leads to an intake of water that is in excess of the free water excreted. This increase in water ingested may then contribute to the maintenance of hyponatremia.
Before the diagnosis of SIADH is made, other causes for a decreased diluting capacity (eg, renal, pituitary, adrenal, thyroid, cardiac, or hepatic disease) must be excluded. In addition, nonosmotic stimuli for arginine vasopressin release, particularly hemodynamic derangements (eg, due to hypotension, nausea, uncontrolled pain, or drugs) must be excluded.
Frequency
United States
SIADH is usually observed in patients in hospital settings, and the frequency may be as high as 35%.
Mortality/Morbidity
The mortality rate for acute symptomatic hyponatremia has been noted to be as high as 55% and as low as 5%, depending on the reference source. The mortality rate associated with chronic hyponatremia has been reported to be 14-27%.
In a retrospective case note review by Clayton and colleagues, patients with a multifactorial cause for hyponatremia in an inpatient setting had a significantly higher mortality rate. The outcome was least favorable in patients who were normonatremic at admission and became hyponatremic during the course of their hospitalization. The etiology of hyponatremia was a more important prognostic indicator than the level of absolute serum sodium in the patients.
Water balance is an important regulatory function involving the hypothalamus and the kidneys (among other organs). Various hormones are also involved, of which the antidiuretic hormone (ADH) arginine vasopressin is most important.
The syndrome of inappropriate secretion of ADH (SIADH) is characterized by the nonphysiologic release of ADH, resulting in impaired water excretion with normal sodium excretion.
SIADH was first described by Schwartz and associates in 2 patients with bronchogenic carcinoma and was later further characterized by Bartter and Schwartz.
Pathophysiology
ADH is a polypeptide synthesized in the supraoptic and paraventricular nuclei in the hypothalamus and is released in response to a number of stimuli. ADH is rapidly metabolized in the liver and kidneys and has a half-life of 15-20 minutes.
In the kidneys, ADH acts on the principal cells of the cortical and medullary collecting tubules to increase water permeability. Other renal actions include local production of prostaglandins in a variety of renal cells, including the glomerulus and the thick ascending limb of the loop of Henle. Elsewhere, ADH causes vasoconstriction in a number of vascular beds and releases factor VIII and von Willebrand factor from vascular endothelium.
Three known receptors bind ADH at the cell membrane: V1a, V1b (also known as V3), and V2. The vasopressin (AVP, ADH) receptor subtypes belong to the G protein–coupled receptor superfamily. The V1a and V1b receptors signal by activation of phospholipase C and elevation in intracellular calcium, which, in turn, stimulates protein kinase C.
V1a subtype is ubiquitous and found on cells, such as vascular smooth muscle cells, hepatocytes, platelets, brain cells, and uterus cells. V1b receptors are found predominantly in the anterior pituitary.
V2 receptors are coupled to adenylate cyclase, causing a rise in intracellular cyclic adenosine monophosphate (cAMP), which serves as the second messenger. V2 receptors are found predominantly in the principal cells of the renal collecting duct, where they mediate antidiuretic response. V2 receptors are also found in endothelial cells and induce the secretion of von Willebrand factor.
ADH activates the V2 receptor on the basolateral membrane of the principal cells of the renal collecting duct. This activates cyclic adenosine monophosphate through heterotrimeric G proteins, which results in insertion of aquaporin-2 water channels in the luminal membrane, thus making it more permeable to water.
The major stimuli to ADH are hyperosmolality and effective circulating volume depletion. Normally, ADH secretion ceases when plasma osmolality falls below 275 mOsm/kg. This fall causes increased water excretion, which leads to a dilute urine with an osmolality of 40-100 mOsm/kg. In addition to the hypothalamic osmoreceptors, hypothalamic neurons secreting ADH also receive input from baroreceptors in the great vessels and the atria. This results in nonosmotic release of ADH. Other stimuli for ADH secretion include pain and nausea.
In general, the plasma sodium concentration is the primary osmotic determinant of ADH release. However, in persons with SIADH, a nonphysiologic secretion of ADH results in enhanced water reabsorption, leading to dilutional hyponatremia. Sodium excretion is intact, and the amount of sodium excreted in the urine varies with diet. Ingestion of water is an essential prerequisite to the development of dilutional hyponatremia; regardless of cause, hyponatremia does not occur if water is restricted.
The continued presence of ADH with water intake causes retention of ingested water. While a large fraction of this water is intracellular, the extracellular fraction causes volume expansion. Volume receptors are activated and peptides (eg, atrial natriuretic peptide) are secreted, which causes natriuresis with some degree of accompanying kaliuresis and diuresis. Thus, these patients are euvolemic or are slightly volume-expanded.
If water and sodium intake remain constant, a steady state is reached and sodium excretion equals sodium intake. Experimental evidence indicates that several days after ADH-induced water retention, escape from its effect occurs. This results in the establishment of a water balance and a newer, stable (although lower) sodium concentration. This is thought to be mediated via pressure-induced natriuresis and diuresis. Other authorities attribute this escape phenomenon to a decrease in the aquaporin-2 channel expression in the renal collecting duct.
In addition to the inappropriate ADH secretion, persons with this syndrome also may have an inappropriate thirst sensation, which leads to an intake of water that is in excess of the free water excreted. This increase in water ingested may then contribute to the maintenance of hyponatremia.
Before the diagnosis of SIADH is made, other causes for a decreased diluting capacity (eg, renal, pituitary, adrenal, thyroid, cardiac, or hepatic disease) must be excluded. In addition, nonosmotic stimuli for arginine vasopressin release, particularly hemodynamic derangements (eg, due to hypotension, nausea, uncontrolled pain, or drugs) must be excluded.
Frequency
United States
SIADH is usually observed in patients in hospital settings, and the frequency may be as high as 35%.
Mortality/Morbidity
The mortality rate for acute symptomatic hyponatremia has been noted to be as high as 55% and as low as 5%, depending on the reference source. The mortality rate associated with chronic hyponatremia has been reported to be 14-27%.
In a retrospective case note review by Clayton and colleagues, patients with a multifactorial cause for hyponatremia in an inpatient setting had a significantly higher mortality rate. The outcome was least favorable in patients who were normonatremic at admission and became hyponatremic during the course of their hospitalization. The etiology of hyponatremia was a more important prognostic indicator than the level of absolute serum sodium in the patients.
Wednesday 18 June 2008
Azotemia
Background
Each human kidney contains approximately 1 million functional units, called nephrons, which are primarily involved in formation. Formation ensures that the body eliminates the final products of metabolic activities and excess water in an attempt to maintain a constant internal environment (homeostasis).
Urine formation by each nephron involves 3 main processes, as follows: filtration at the glomerular level, selective reabsorption from the filtrate passing along the renal tubules, and secretion by the cells of the tubules into this filtrate. Perturbation of any of these processes impairs the kidney's excretory function, resulting in azotemia, which is elevation of blood urea nitrogen (BUN) (reference range, 8-20 mg/dL) and serum creatinine (normal value, 0.7-1.4 mg/dL) levels.
The quantity of glomerular filtrate produced each minute by all nephrons in both kidneys is referred to as the glomerular filtration rate (GFR). Average GFR is about 125 mL/min (10% less for women) or 180 L/d. About 99% (178 L/d) is reabsorbed, and the rest (2 L/d) is excreted.
Measuring renal function
Radionuclide assessment of GFR is the criterion standard for measuring kidney function. However, because it is expensive and not widely available, serum creatinine concentration and creatinine clearance (CrCl) more commonly are used.
An inverse relationship between serum creatinine and GFR exists. However, the serum creatinine and CrCl are not sensitive measures of kidney damage for two reasons. First, substantial renal damage can take place before any decrease in GFR occurs. Second, a substantial decline in GFR may lead to only slight elevation in serum creatinine, as shown in Media file 1. An elevation in serum creatinine is apparent only when the GFR falls to about 60-70 mL/min. This is due to compensatory hypertrophy and hyperfiltration of the remaining healthy nephrons.
Because creatinine normally is filtered as well as secreted into the renal tubules, the CrCl may cause the GFR to be substantially overestimated, especially as kidney failure progresses because of maximal tubular excretion. More accurate determinations of GFR require the use of inulin clearance or a radiolabeled compound, such as iothalamate. In practice, precise knowledge of the GFR is not required, and disease process usually can be monitored by the estimated GFR (eGFR) using different methods, as shown below.
The CrCl is best calculated by obtaining a 24-hour collection for creatinine and volume and then using the following formula: CrCl (mL/min) = U/P X V where U is the 24-hour creatinine in mg/dL, P is the serum creatinine in mg/dL, and V is the 24-hour volume/1440 (number of min in 24 h). Using the 24-hour creatinine in grams and the serum creatinine in milligrams, CrCl (mL/min) = creatinine [g/d]/serum creatinine [mg/dL]) X 70. An adequate 24-hour collection usually reflects a creatinine generation of 15-20 mg/kg in women and 20-25 mg/kg in men. When 24-hour creatinine is measured, the adequacy of the collection must be established prior to calculation of the creatinine clearance.
Alternatively, a bedside formula (Cockroft and Gault) using the patient's serum creatinine, age, and lean weight (in kg) can be used to estimate the GFR, as follows: CrCl (mL/min) = (140 - age) X weight (kg) / (72 X serum creatinine) in mg/dL (X 0.85 for women).Another formula was derived from data collected in a large study called the Modification of Diet in Renal Disease (MDRD). This formula is known as the MDRD formula or the Levey formula. It is now widely accepted as more accurate than the Cockroft and Gault formula and is an alternative to radioisotope clearance. Because serum creatinine levels alone cannot detect earlier stages of chronic kidney disease (CKD), the MDRD formula also takes into account the patient's age and race. Although more accurate, it is much more difficult to calculate manually. However, software for estimating GFR by the MDRD formula is available on most pocket digital assistants (PDA) or can be found on the Internet.
Pathophysiology
There are three pathophysiologic states in azotemia, as follows: prerenal azotemia, intrarenal azotemia, and postrenal azotemia.
Prerenal azotemia
Prerenal azotemia refers to elevation in BUN and creatinine levels because of problems in the systemic circulation that decrease flow to the kidneys. In prerenal azotemia, decrease in renal flow stimulates salt and water retention to restore volume and pressure. When volume or pressure is decreased, the baroreceptor reflexes located in the aortic arch and carotid sinuses are activated. This leads to sympathetic nerve activation, resulting in renal afferent arteriolar vasoconstriction and renin secretion through b1-receptors. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure, reducing GFR proportionally. Renin converts angiotensin I to angiotensin II, which, in turn, stimulates aldosterone release. Increased aldosterone levels results in salt and water absorption in the distal collecting tubule.
A decrease in volume or pressure is a nonosmotic stimulus for antidiuretic hormone production in the hypothalamus, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as BUN, creatinine, calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (<20 mEq/L).
Intrarenal azotemia
Intrarenal azotemia, also known as acute renal failure (ARF), renal-renal azotemia, and acute kidney injury (AKI), refers to elevation in BUN and creatinine levels because of problems in the kidney itself. There are several definitions, including a rise in serum creatinine levels of about 30% from baseline or a sudden decline in output below 500 mL/d. If output is preserved, it is called nonoliguric ARF. If output falls below 500 mL/d, it is called oliguric ARF. Any form of ARF may be so severe to virtually stop formation, a condition called anuria (<100 mL/d).
The most common causes of nonoliguric ARF are acute tubular necrosis (ATN), aminoglycoside nephrotoxicity, lithium toxicity, or cisplatin nephrotoxicity. Tubular damage is less severe than in oliguric ARF. Normal output in nonoliguric ARF does not reflect normal GFR. Patients may still make 1440 mL/d of urine even when the GFR falls to about 1 mL/min because of decreased tubular reabsorption.
Some studies indicate that nonoliguric forms of ARF are associated with less morbidity and mortality than oliguric ARF. Uncontrolled studies also suggest that volume expansion, potent diuretic agents, and renal vasodilators can convert oliguric to nonoliguric ARF if administered early.
The pathophysiology of acute oliguric or nonoliguric ARF depends on the anatomical location of the injury. In ATN, epithelial damage leads to functional decline in the ability of the tubules to reabsorb salt, water, and other electrolytes. Excretion of acid and potassium also is impaired. In more severe ATN, the tubular lumen is filled with epithelial casts, causing intraluminal obstruction, resulting in the decline of GFR.
Acute interstitial nephritis is characterized by inflammation and edema, resulting in azotemia, hematuria, sterile pyuria, white cell casts with variable eosinophiluria, proteinuria, and hyaline casts. The net effect is a loss of urinary concentrating ability, with low osmolality (usually <500>40 mEq/L), and, occasionally, hyperkalemia and renal tubular acidosis. However, in the presence of a superimposed prerenal azotemia, the specific gravity, osmolality, and sodium may be misleading.
Glomerulonephritis or vasculitis is suggested by the presence of hematuria, red cells, white cells, granular and cellular casts, and a variable degree of proteinuria. Nephrotic syndrome usually is not associated with active inflammation and often presents as proteinuria greater than 3.5 g/24 h.
Glomerular diseases may reduce GFR due to changes in basement membrane permeability, as well as stimulation of the renin-aldosterone axis. Glomerular diseases often manifest as nephrotic or nephric syndrome. In nephrotic syndrome, the urinary sediment is inactive, and there is gross proteinuria (>3.5 g/d), hypoalbuminemia, hyperlipidemia, and edema. Azotemia and hypertension are uncommon initially, but their presence may indicate advanced disease.
In nephritic syndrome, the urinary sediment is active with white or red cell casts, granular casts, and azotemia. Proteinuria is less obvious, but increased salt and water retention in glomerulnephritis can lead to hypertension, edema formation, decreased output, low urinary excretion of sodium, and increased specific gravity.
Acute vascular diseases include vasculitis syndromes, malignant hypertension, scleroderma renal crisis, and thromboembolic disease, all of which cause renal hypoperfusion and ischemia leading to azotemia. Chronic vascular diseases are due to hypertensive benign nephrosclerosis, which has not been conclusively associated with end-stage renal disease and ischemic renal disease from bilateral renal artery stenosis.
In bilateral renal artery stenosis, maintenance of adequate intraglomerular pressure for filtration greatly depends on efferent arteriolar vasoconstriction. Azotemia sets in when angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 2 receptor blockers cause efferent arteriolar dilatation, thereby decreasing intraglomerular pressure and filtration. Therefore, converting enzyme inhibitors and receptor blockers are contraindicated in bilateral renal artery stenosis.
In addition to accumulation of urea creatinine and other waste products, a substantial reduction in GFR in CKD results in decreased production of erythropoietin (causing anemia) and vitamin D-3 (causing hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, and renal osteodystrophy); reduction in acid, potassium, salt, and water excretion (causing acidosis, hyperkalemia, hypertension, and edema); and platelet dysfunction, which leads to increased bleeding tendencies.
The syndrome associated with the signs and symptoms of accumulation of toxic waste products (uremic toxins) is termed uremia and often occurs at a GFR of about 10 mL/min. Some of the uremic toxins (ie, urea, creatinine, phenols, guanidines) have been identified, but none has been found responsible for all the manifestations of uremia.
Postrenal azotemia
Postrenal azotemia refers to elevation in BUN and creatinine levels because of obstruction in the collecting system. Obstruction to flow leads to a reversal of Starling forces responsible for glomerular filtration. Progressive bilateral obstruction causes hydronephrosis with an increase in the Bowman capsular hydrostatic pressure and tubular blockage resulting in progressive decline and ultimate cessation in glomerular filtration, azotemia, acidosis, fluid overload, and hyperkalemia.
Unilateral obstruction rarely causes azotemia. With relief of complete ureteral obstruction within 48 hours of onset, there is evidence that relatively complete recovery of GFR can be achieved within a week, while little or no further recovery occurs after 12 weeks. Complete or prolonged partial obstruction can lead to tubular atrophy and irreversible renal fibrosis. Hydronephrosis may be absent if obstruction is mild or acute or if the collecting system is encased by retroperitoneal tumor or fibrosis.
Frequency
United States
Considerable variability exists in reports about the incidence of hospital or community-acquired ARF. In one report, community-acquired ARF occurred in about 1% of all hospital admissions. Overall, ARF occurs in about 5% of all hospital admissions. However, differences exist in ARF occurring in the intensive care unit (about 15%) and in the coronary care unit (about 4%). In CKD, progressive azotemia leading to end-stage renal disease requiring dialysis or kidney transplantation occurs in a number of chronic diseases with frequencies for diabetes (36%), hypertension (24%), glomerulonephritis (15%), cystic kidney disease (4%), uncertain (5%), and all other known miscellaneous renal disorders (15%).
International
A report from Madrid evaluated 748 cases of ARF at 13 tertiary hospital centers. The most frequent causes were ATN (45%); prerenal (21%); acute or chronic renal failure, mostly due to ATN and prerenal disease (13%); urinary tract obstruction (10%); glomerulonephritis or vasculitis (4%); acute interstitial nephritis (2%); and atheroemboli (1%). Etiologies of CKD differ around the world. Diabetic nephropathy as a cause of CKD is on the rise in developed and developing countries.
Mortality/Morbidity
Prognosis in ARF generally is poor and depends on the severity of the underlying disease and the number of failed organs. While mortality rate in simple ARF without other underlying disease is 7-23%, the mortality in the patient in the intensive care unit on mechanical ventilation is as high as 80%.
The prognosis of patients with CKD depends on the etiology of the failure. Patients with diabetic kidney disease, hypertensive nephrosclerosis, and ischemic nephropathy (ie, large-vessel arterial occlusive disease) tend to have progressive azotemia resulting in end-stage renal disease. Different types of glomerulonephritis have major differences in prognosis, with some being quite benign and rarely progressing to end-stage renal disease, whereas others have rapid progression to end-stage renal disease within months. About 50% of patients with polycystic kidney disease progress to end-stage renal disease by the fifth or sixth decade of life.
Race
In the 2006 annual report of the United States Renal Data System (USRDS), more than 500,000 patients with end-stage renal disease were receiving dialysis or a kidney transplant in the United States. Racial distribution was reported as Asian/Pacific Islander (4.0%), black (33.0%), white (61.0%), American Indian (1.3%), and other/unknown (1.7%).
Sex
Of the patients reported in the 2006 annual report of the USRDS, male frequency is 56.0% and female frequency is 44.0%.
Age
Of the patients reported in the 2006 annual report of the USRDS, frequencies for patients aged 0-19 years is 1%; aged 20-44 years, 17.0%; aged 45-64 years, 41.0%; aged 65-74 years, 22.0%; and older than 75 years, 18.0%.
Read more HERE
Each human kidney contains approximately 1 million functional units, called nephrons, which are primarily involved in formation. Formation ensures that the body eliminates the final products of metabolic activities and excess water in an attempt to maintain a constant internal environment (homeostasis).
Urine formation by each nephron involves 3 main processes, as follows: filtration at the glomerular level, selective reabsorption from the filtrate passing along the renal tubules, and secretion by the cells of the tubules into this filtrate. Perturbation of any of these processes impairs the kidney's excretory function, resulting in azotemia, which is elevation of blood urea nitrogen (BUN) (reference range, 8-20 mg/dL) and serum creatinine (normal value, 0.7-1.4 mg/dL) levels.
The quantity of glomerular filtrate produced each minute by all nephrons in both kidneys is referred to as the glomerular filtration rate (GFR). Average GFR is about 125 mL/min (10% less for women) or 180 L/d. About 99% (178 L/d) is reabsorbed, and the rest (2 L/d) is excreted.
Measuring renal function
Radionuclide assessment of GFR is the criterion standard for measuring kidney function. However, because it is expensive and not widely available, serum creatinine concentration and creatinine clearance (CrCl) more commonly are used.
An inverse relationship between serum creatinine and GFR exists. However, the serum creatinine and CrCl are not sensitive measures of kidney damage for two reasons. First, substantial renal damage can take place before any decrease in GFR occurs. Second, a substantial decline in GFR may lead to only slight elevation in serum creatinine, as shown in Media file 1. An elevation in serum creatinine is apparent only when the GFR falls to about 60-70 mL/min. This is due to compensatory hypertrophy and hyperfiltration of the remaining healthy nephrons.
Because creatinine normally is filtered as well as secreted into the renal tubules, the CrCl may cause the GFR to be substantially overestimated, especially as kidney failure progresses because of maximal tubular excretion. More accurate determinations of GFR require the use of inulin clearance or a radiolabeled compound, such as iothalamate. In practice, precise knowledge of the GFR is not required, and disease process usually can be monitored by the estimated GFR (eGFR) using different methods, as shown below.
The CrCl is best calculated by obtaining a 24-hour collection for creatinine and volume and then using the following formula: CrCl (mL/min) = U/P X V where U is the 24-hour creatinine in mg/dL, P is the serum creatinine in mg/dL, and V is the 24-hour volume/1440 (number of min in 24 h). Using the 24-hour creatinine in grams and the serum creatinine in milligrams, CrCl (mL/min) = creatinine [g/d]/serum creatinine [mg/dL]) X 70. An adequate 24-hour collection usually reflects a creatinine generation of 15-20 mg/kg in women and 20-25 mg/kg in men. When 24-hour creatinine is measured, the adequacy of the collection must be established prior to calculation of the creatinine clearance.
Alternatively, a bedside formula (Cockroft and Gault) using the patient's serum creatinine, age, and lean weight (in kg) can be used to estimate the GFR, as follows: CrCl (mL/min) = (140 - age) X weight (kg) / (72 X serum creatinine) in mg/dL (X 0.85 for women).Another formula was derived from data collected in a large study called the Modification of Diet in Renal Disease (MDRD). This formula is known as the MDRD formula or the Levey formula. It is now widely accepted as more accurate than the Cockroft and Gault formula and is an alternative to radioisotope clearance. Because serum creatinine levels alone cannot detect earlier stages of chronic kidney disease (CKD), the MDRD formula also takes into account the patient's age and race. Although more accurate, it is much more difficult to calculate manually. However, software for estimating GFR by the MDRD formula is available on most pocket digital assistants (PDA) or can be found on the Internet.
Pathophysiology
There are three pathophysiologic states in azotemia, as follows: prerenal azotemia, intrarenal azotemia, and postrenal azotemia.
Prerenal azotemia
Prerenal azotemia refers to elevation in BUN and creatinine levels because of problems in the systemic circulation that decrease flow to the kidneys. In prerenal azotemia, decrease in renal flow stimulates salt and water retention to restore volume and pressure. When volume or pressure is decreased, the baroreceptor reflexes located in the aortic arch and carotid sinuses are activated. This leads to sympathetic nerve activation, resulting in renal afferent arteriolar vasoconstriction and renin secretion through b1-receptors. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure, reducing GFR proportionally. Renin converts angiotensin I to angiotensin II, which, in turn, stimulates aldosterone release. Increased aldosterone levels results in salt and water absorption in the distal collecting tubule.
A decrease in volume or pressure is a nonosmotic stimulus for antidiuretic hormone production in the hypothalamus, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as BUN, creatinine, calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (<20 mEq/L).
Intrarenal azotemia
Intrarenal azotemia, also known as acute renal failure (ARF), renal-renal azotemia, and acute kidney injury (AKI), refers to elevation in BUN and creatinine levels because of problems in the kidney itself. There are several definitions, including a rise in serum creatinine levels of about 30% from baseline or a sudden decline in output below 500 mL/d. If output is preserved, it is called nonoliguric ARF. If output falls below 500 mL/d, it is called oliguric ARF. Any form of ARF may be so severe to virtually stop formation, a condition called anuria (<100 mL/d).
The most common causes of nonoliguric ARF are acute tubular necrosis (ATN), aminoglycoside nephrotoxicity, lithium toxicity, or cisplatin nephrotoxicity. Tubular damage is less severe than in oliguric ARF. Normal output in nonoliguric ARF does not reflect normal GFR. Patients may still make 1440 mL/d of urine even when the GFR falls to about 1 mL/min because of decreased tubular reabsorption.
Some studies indicate that nonoliguric forms of ARF are associated with less morbidity and mortality than oliguric ARF. Uncontrolled studies also suggest that volume expansion, potent diuretic agents, and renal vasodilators can convert oliguric to nonoliguric ARF if administered early.
The pathophysiology of acute oliguric or nonoliguric ARF depends on the anatomical location of the injury. In ATN, epithelial damage leads to functional decline in the ability of the tubules to reabsorb salt, water, and other electrolytes. Excretion of acid and potassium also is impaired. In more severe ATN, the tubular lumen is filled with epithelial casts, causing intraluminal obstruction, resulting in the decline of GFR.
Acute interstitial nephritis is characterized by inflammation and edema, resulting in azotemia, hematuria, sterile pyuria, white cell casts with variable eosinophiluria, proteinuria, and hyaline casts. The net effect is a loss of urinary concentrating ability, with low osmolality (usually <500>40 mEq/L), and, occasionally, hyperkalemia and renal tubular acidosis. However, in the presence of a superimposed prerenal azotemia, the specific gravity, osmolality, and sodium may be misleading.
Glomerulonephritis or vasculitis is suggested by the presence of hematuria, red cells, white cells, granular and cellular casts, and a variable degree of proteinuria. Nephrotic syndrome usually is not associated with active inflammation and often presents as proteinuria greater than 3.5 g/24 h.
Glomerular diseases may reduce GFR due to changes in basement membrane permeability, as well as stimulation of the renin-aldosterone axis. Glomerular diseases often manifest as nephrotic or nephric syndrome. In nephrotic syndrome, the urinary sediment is inactive, and there is gross proteinuria (>3.5 g/d), hypoalbuminemia, hyperlipidemia, and edema. Azotemia and hypertension are uncommon initially, but their presence may indicate advanced disease.
In nephritic syndrome, the urinary sediment is active with white or red cell casts, granular casts, and azotemia. Proteinuria is less obvious, but increased salt and water retention in glomerulnephritis can lead to hypertension, edema formation, decreased output, low urinary excretion of sodium, and increased specific gravity.
Acute vascular diseases include vasculitis syndromes, malignant hypertension, scleroderma renal crisis, and thromboembolic disease, all of which cause renal hypoperfusion and ischemia leading to azotemia. Chronic vascular diseases are due to hypertensive benign nephrosclerosis, which has not been conclusively associated with end-stage renal disease and ischemic renal disease from bilateral renal artery stenosis.
In bilateral renal artery stenosis, maintenance of adequate intraglomerular pressure for filtration greatly depends on efferent arteriolar vasoconstriction. Azotemia sets in when angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 2 receptor blockers cause efferent arteriolar dilatation, thereby decreasing intraglomerular pressure and filtration. Therefore, converting enzyme inhibitors and receptor blockers are contraindicated in bilateral renal artery stenosis.
In addition to accumulation of urea creatinine and other waste products, a substantial reduction in GFR in CKD results in decreased production of erythropoietin (causing anemia) and vitamin D-3 (causing hypocalcemia, secondary hyperparathyroidism, hyperphosphatemia, and renal osteodystrophy); reduction in acid, potassium, salt, and water excretion (causing acidosis, hyperkalemia, hypertension, and edema); and platelet dysfunction, which leads to increased bleeding tendencies.
The syndrome associated with the signs and symptoms of accumulation of toxic waste products (uremic toxins) is termed uremia and often occurs at a GFR of about 10 mL/min. Some of the uremic toxins (ie, urea, creatinine, phenols, guanidines) have been identified, but none has been found responsible for all the manifestations of uremia.
Postrenal azotemia
Postrenal azotemia refers to elevation in BUN and creatinine levels because of obstruction in the collecting system. Obstruction to flow leads to a reversal of Starling forces responsible for glomerular filtration. Progressive bilateral obstruction causes hydronephrosis with an increase in the Bowman capsular hydrostatic pressure and tubular blockage resulting in progressive decline and ultimate cessation in glomerular filtration, azotemia, acidosis, fluid overload, and hyperkalemia.
Unilateral obstruction rarely causes azotemia. With relief of complete ureteral obstruction within 48 hours of onset, there is evidence that relatively complete recovery of GFR can be achieved within a week, while little or no further recovery occurs after 12 weeks. Complete or prolonged partial obstruction can lead to tubular atrophy and irreversible renal fibrosis. Hydronephrosis may be absent if obstruction is mild or acute or if the collecting system is encased by retroperitoneal tumor or fibrosis.
Frequency
United States
Considerable variability exists in reports about the incidence of hospital or community-acquired ARF. In one report, community-acquired ARF occurred in about 1% of all hospital admissions. Overall, ARF occurs in about 5% of all hospital admissions. However, differences exist in ARF occurring in the intensive care unit (about 15%) and in the coronary care unit (about 4%). In CKD, progressive azotemia leading to end-stage renal disease requiring dialysis or kidney transplantation occurs in a number of chronic diseases with frequencies for diabetes (36%), hypertension (24%), glomerulonephritis (15%), cystic kidney disease (4%), uncertain (5%), and all other known miscellaneous renal disorders (15%).
International
A report from Madrid evaluated 748 cases of ARF at 13 tertiary hospital centers. The most frequent causes were ATN (45%); prerenal (21%); acute or chronic renal failure, mostly due to ATN and prerenal disease (13%); urinary tract obstruction (10%); glomerulonephritis or vasculitis (4%); acute interstitial nephritis (2%); and atheroemboli (1%). Etiologies of CKD differ around the world. Diabetic nephropathy as a cause of CKD is on the rise in developed and developing countries.
Mortality/Morbidity
Prognosis in ARF generally is poor and depends on the severity of the underlying disease and the number of failed organs. While mortality rate in simple ARF without other underlying disease is 7-23%, the mortality in the patient in the intensive care unit on mechanical ventilation is as high as 80%.
The prognosis of patients with CKD depends on the etiology of the failure. Patients with diabetic kidney disease, hypertensive nephrosclerosis, and ischemic nephropathy (ie, large-vessel arterial occlusive disease) tend to have progressive azotemia resulting in end-stage renal disease. Different types of glomerulonephritis have major differences in prognosis, with some being quite benign and rarely progressing to end-stage renal disease, whereas others have rapid progression to end-stage renal disease within months. About 50% of patients with polycystic kidney disease progress to end-stage renal disease by the fifth or sixth decade of life.
Race
In the 2006 annual report of the United States Renal Data System (USRDS), more than 500,000 patients with end-stage renal disease were receiving dialysis or a kidney transplant in the United States. Racial distribution was reported as Asian/Pacific Islander (4.0%), black (33.0%), white (61.0%), American Indian (1.3%), and other/unknown (1.7%).
Sex
Of the patients reported in the 2006 annual report of the USRDS, male frequency is 56.0% and female frequency is 44.0%.
Age
Of the patients reported in the 2006 annual report of the USRDS, frequencies for patients aged 0-19 years is 1%; aged 20-44 years, 17.0%; aged 45-64 years, 41.0%; aged 65-74 years, 22.0%; and older than 75 years, 18.0%.
Read more HERE
Tuesday 17 June 2008
Rheumatoid Arthritis
Background
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease characterized by synovitis and serositis (inflammation of the lining surfaces of the joints, pericardium, and pleura), rheumatoid nodules, and vasculitis. The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that affects the hands and feet, although any joint lined by a synovial membrane may be involved. In addition to articular deterioration, systemic involvement may lead to weight loss, low-grade fever, and malaise. The severity of RA may fluctuate over time, but chronic RA most commonly results in the progressive development of various degrees of joint destruction, deformity, and a significant decline in functional status.
Juvenile rheumatoid arthritis (JRA) is the most common form of childhood arthritis. The cause remains unknown. For most patients, the immunogenic associations, clinical pattern, and functional outcome are different from adult onset RA.
The diagnostic criteria for JRA are onset occurring when younger than 16 years, persistent arthritis in one or more joints for at least 6 weeks, and exclusion of other types of childhood arthritis. The key points that characterize the diagnosis of JRA are as follows:
Arthritis must be present. Arthritis is defined as the presence of swelling, the presence of effusion, or the presence of 2 or more of the following signs: limited range of motion (ROM), tenderness, pain on motion, or joint warmth.
Arthritis must persist for at least 6 weeks.
Other causes of chronic arthritis in children must be ruled out.
No specific laboratory or other test can establish the diagnosis of JRA.
Pathophysiology
The diagnosis of RA must be considered in any patient with polyarticular inflammatory arthritis, especially if both the hands and feet are involved. The early phase of the disease is characterized by the following features:
Joint swelling that may affect joint margins
Joint tenderness upon palpation
Systemic malaise
Loss of energy
Severe morning stiffness that limits function and generally lasts more than an hour
A classic feature of the illness is the symmetry of involvement. If synovial-based inflammation persists over time, permanent damage to tendons, ligaments, and cartilage and subchondral bone destruction occur with resultant joint deformity and limited motion. Inflammation and deformity also are nearly always seen in the hands and feet. However, involvement of the knees, hips, and shoulders accounts for significant morbidity that leads to work disability in a large percentage of patients.
A major difference in the pathophysiology of RA versus osteoarthritis or mechanical joint problems is the presence of extensive synovial inflammation. The characteristic signs of inflammation were stated by Celsus as "rubor et tumor cum calore et dolore," meaning redness and swelling with heat and pain. Galen later added "et functio laesa" (disturbed function) to the characteristic signs of inflammation. Joint tenderness, swelling, stiffness, and pain on motion are the features of inflammation experienced by patients with RA.
Frequency
United States
The prevalence rate of RA is approximately 1% of the population (range 0.3-2.1%).
Race
RA is observed throughout the world and affects persons of all races.
Sex
Women are affected approximately 3 times more often than men. Sex differences diminish in older age groups.
Age
Although RA can occur at any age, the incidence increases with advancing age. The peak incidence of RA occurs in individuals aged 40-60 years.
Read more HERE
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease characterized by synovitis and serositis (inflammation of the lining surfaces of the joints, pericardium, and pleura), rheumatoid nodules, and vasculitis. The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that affects the hands and feet, although any joint lined by a synovial membrane may be involved. In addition to articular deterioration, systemic involvement may lead to weight loss, low-grade fever, and malaise. The severity of RA may fluctuate over time, but chronic RA most commonly results in the progressive development of various degrees of joint destruction, deformity, and a significant decline in functional status.
Juvenile rheumatoid arthritis (JRA) is the most common form of childhood arthritis. The cause remains unknown. For most patients, the immunogenic associations, clinical pattern, and functional outcome are different from adult onset RA.
The diagnostic criteria for JRA are onset occurring when younger than 16 years, persistent arthritis in one or more joints for at least 6 weeks, and exclusion of other types of childhood arthritis. The key points that characterize the diagnosis of JRA are as follows:
Arthritis must be present. Arthritis is defined as the presence of swelling, the presence of effusion, or the presence of 2 or more of the following signs: limited range of motion (ROM), tenderness, pain on motion, or joint warmth.
Arthritis must persist for at least 6 weeks.
Other causes of chronic arthritis in children must be ruled out.
No specific laboratory or other test can establish the diagnosis of JRA.
Pathophysiology
The diagnosis of RA must be considered in any patient with polyarticular inflammatory arthritis, especially if both the hands and feet are involved. The early phase of the disease is characterized by the following features:
Joint swelling that may affect joint margins
Joint tenderness upon palpation
Systemic malaise
Loss of energy
Severe morning stiffness that limits function and generally lasts more than an hour
A classic feature of the illness is the symmetry of involvement. If synovial-based inflammation persists over time, permanent damage to tendons, ligaments, and cartilage and subchondral bone destruction occur with resultant joint deformity and limited motion. Inflammation and deformity also are nearly always seen in the hands and feet. However, involvement of the knees, hips, and shoulders accounts for significant morbidity that leads to work disability in a large percentage of patients.
A major difference in the pathophysiology of RA versus osteoarthritis or mechanical joint problems is the presence of extensive synovial inflammation. The characteristic signs of inflammation were stated by Celsus as "rubor et tumor cum calore et dolore," meaning redness and swelling with heat and pain. Galen later added "et functio laesa" (disturbed function) to the characteristic signs of inflammation. Joint tenderness, swelling, stiffness, and pain on motion are the features of inflammation experienced by patients with RA.
Frequency
United States
The prevalence rate of RA is approximately 1% of the population (range 0.3-2.1%).
Race
RA is observed throughout the world and affects persons of all races.
Sex
Women are affected approximately 3 times more often than men. Sex differences diminish in older age groups.
Age
Although RA can occur at any age, the incidence increases with advancing age. The peak incidence of RA occurs in individuals aged 40-60 years.
Read more HERE
Saturday 7 June 2008
Osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by decreased bone mass and deterioration of bony microarchitecture. The result is fragile bones and an increased risk for fracture with even minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. Osteoporosis is a significant health problem in the United States and around the world.
Pathophysiology: Osteoporosis results from a combination of genetic and environmental factors that affect both peak bone mass and the rate of bone loss. These factors include medications, diet, race, sex, lifestyle, and physical activity. Osteoporosis may be either primary or secondary. Primary osteoporosis is subdivided into types 1 and 2. Secondary osteoporosis is also called type 3.
Type 1, or postmenopausal, osteoporosis is thought to result from gonadal (ie, estrogen, testosterone) deficiency. Estrogen or testosterone deficiency, regardless of age of occurrence, results in accelerated bone loss. The exact mechanisms of this bone loss potentially are numerous, but, ultimately, an increased recruitment and responsiveness of osteoclast precursors and an increase in bone resorption, which outpaces bone formation, occurs. After menopause, women experience an accelerated bone loss of 1-5% per year for the first 5-7 years. The end result is a decrease in trabecular bone and an increased risk of Colles and vertebral fractures.
Evidence indicates that estrogen deficiency causes bone to become more sensitive to the effects of parathyroid hormone (PTH), leading to an increase in calcium release from bone, a decrease in renal calcium excretion, and increased production of 1,25-dihydroxyvitamin D (1,25[OH]2 D3). Increased production of 1,25(OH)2 D3, in turn, causes increased calcium absorption from the gut, increased calcium resorption from bone, and increased renal tubular calcium resorption. PTH secretion then decreases via a negative feedback effect, causing the opposite effects. Osteoclasts are also influenced by cytokines, such as tumor necrosis factor-alpha and interleukins 1 and 6, whose production by mononuclear cells may be increased in the presence of gonadal deficiency.
Type 2, or senile, osteoporosis occurs in women and men because of decreased formation of bone and decreased renal production of 1,25(OH)2 D3 occurring late in life. The consequence is a loss of cortical and trabecular bone and increased risk for fractures of the hip, long bones, and vertebrae.
Type 3 osteoporosis occurs secondary to medications, especially glucocorticoids, or other conditions that cause increased bone loss by various mechanisms.
Frequency:
In the US: Approximately 10 million people have osteoporosis. Another 14-18 million have osteopenia (low bone mass).
Internationally: According to the International Osteoporosis Foundation, osteoporosis affects approximately 1 in 3 women and 1 in 8 men worldwide.
Mortality/Morbidity:
In Europe, an estimated 1 in 8 persons older than 50 years experiences a spinal fracture, and 1 in 3 women and 1 in 9 men older than 80 years experiences a hip fracture due to osteoporosis.
Approximately 1.5 million fractures per year in the United States are attributed to osteoporosis, and more than 37,000 people die from subsequent fracture-related complications. Among women who sustain a hip fracture, 50% spend time in a nursing home while recovering, and 14% of all patients with hip fractures remain in nursing homes 1 year later.
Only one third of patients return to their prefracture level of function. Patients incur a diminished quality of life and decreased independence in daily living.
Race: Whites, especially of northern European descent, and Asians are at increased risk for osteoporosis.
Sex: In type 1 and type 2 osteoporosis, women are affected more often than men, with female-to-male ratios of 6:2 and 2:1, respectively. In type 3, both sexes are equally affected.
Age: The peak incidence of type 1 osteoporosis is in people aged 50-70 years, and the peak incidence for type 2 is in people aged 70 years or older. Type 3 can occur in persons of any age.
Read more HERE
Pathophysiology: Osteoporosis results from a combination of genetic and environmental factors that affect both peak bone mass and the rate of bone loss. These factors include medications, diet, race, sex, lifestyle, and physical activity. Osteoporosis may be either primary or secondary. Primary osteoporosis is subdivided into types 1 and 2. Secondary osteoporosis is also called type 3.
Type 1, or postmenopausal, osteoporosis is thought to result from gonadal (ie, estrogen, testosterone) deficiency. Estrogen or testosterone deficiency, regardless of age of occurrence, results in accelerated bone loss. The exact mechanisms of this bone loss potentially are numerous, but, ultimately, an increased recruitment and responsiveness of osteoclast precursors and an increase in bone resorption, which outpaces bone formation, occurs. After menopause, women experience an accelerated bone loss of 1-5% per year for the first 5-7 years. The end result is a decrease in trabecular bone and an increased risk of Colles and vertebral fractures.
Evidence indicates that estrogen deficiency causes bone to become more sensitive to the effects of parathyroid hormone (PTH), leading to an increase in calcium release from bone, a decrease in renal calcium excretion, and increased production of 1,25-dihydroxyvitamin D (1,25[OH]2 D3). Increased production of 1,25(OH)2 D3, in turn, causes increased calcium absorption from the gut, increased calcium resorption from bone, and increased renal tubular calcium resorption. PTH secretion then decreases via a negative feedback effect, causing the opposite effects. Osteoclasts are also influenced by cytokines, such as tumor necrosis factor-alpha and interleukins 1 and 6, whose production by mononuclear cells may be increased in the presence of gonadal deficiency.
Type 2, or senile, osteoporosis occurs in women and men because of decreased formation of bone and decreased renal production of 1,25(OH)2 D3 occurring late in life. The consequence is a loss of cortical and trabecular bone and increased risk for fractures of the hip, long bones, and vertebrae.
Type 3 osteoporosis occurs secondary to medications, especially glucocorticoids, or other conditions that cause increased bone loss by various mechanisms.
Frequency:
In the US: Approximately 10 million people have osteoporosis. Another 14-18 million have osteopenia (low bone mass).
Internationally: According to the International Osteoporosis Foundation, osteoporosis affects approximately 1 in 3 women and 1 in 8 men worldwide.
Mortality/Morbidity:
In Europe, an estimated 1 in 8 persons older than 50 years experiences a spinal fracture, and 1 in 3 women and 1 in 9 men older than 80 years experiences a hip fracture due to osteoporosis.
Approximately 1.5 million fractures per year in the United States are attributed to osteoporosis, and more than 37,000 people die from subsequent fracture-related complications. Among women who sustain a hip fracture, 50% spend time in a nursing home while recovering, and 14% of all patients with hip fractures remain in nursing homes 1 year later.
Only one third of patients return to their prefracture level of function. Patients incur a diminished quality of life and decreased independence in daily living.
Race: Whites, especially of northern European descent, and Asians are at increased risk for osteoporosis.
Sex: In type 1 and type 2 osteoporosis, women are affected more often than men, with female-to-male ratios of 6:2 and 2:1, respectively. In type 3, both sexes are equally affected.
Age: The peak incidence of type 1 osteoporosis is in people aged 50-70 years, and the peak incidence for type 2 is in people aged 70 years or older. Type 3 can occur in persons of any age.
Read more HERE
Mitral Regurgitation
Mitral regurgitation, in the acute and chronic decompensated states, is commonly encountered in the emergency department. An understanding of the underlying etiologies and pathophysiology of the condition is critical to direct appropriate treatment.
Pathophysiology
Mitral regurgitation can be divided into the following 3 stages: acute, chronic compensated, and chronic decompensated.
In the acute stage, which usually occurs with a spontaneous chordae tendineae rupture secondary to myocardial infarction, a sudden volume overload occurs on an unprepared left ventricle and left atrium. The volume overload on the left ventricle increases left ventricular stroke work. Increased left ventricular filling pressures, combined with the transfer of blood from the left ventricle to the left atrium during systole, results in elevated left atrial pressures. This increased pressure is transmitted to the lungs resulting in acute pulmonary edema and dyspnea.
If the patient tolerates the acute phase, the chronic compensated phase begins. The chronic compensated phase results in eccentric left ventricular hypertrophy. The combination of increased preload and hypertrophy produces increased end-diastolic volumes, which, over time, result in left ventricular muscle dysfunction. This muscle dysfunction impairs the emptying of the ventricle during systole. Therefore, regurgitant volume and left atrial pressures increase, leading to pulmonary congestion.
Frequency
United States
Previously, chronic rheumatic heart disease was the most common cause of acquired mitral valve disease in the Western world. More recently, however, mitral valve prolapse (MVP) has become the most common cause, being responsible for 45% of cases of mitral regurgitation. MVP has been estimated to be present in 4% of the population; however, significant regurgitation in this population only occurs in those with abnormalities of the valve.
International
In areas other than the Western world, rheumatic heart disease remains the leading cause of mitral regurgitation.
Mortality/Morbidity
The prognosis of patients with mitral regurgitation depends on the underlying etiologies and the state of the left ventricular function.
Acute pulmonary edema and cardiogenic shock often complicate the course of acute regurgitation. The operative mortality in these cases approaches 80%. A patient with ruptured chordae tendineae and minimal symptoms has a much better prognosis.
With chronic regurgitation, volume overload is tolerated very well for years before symptoms of failure develop. Left atrial enlargement predisposes patients to the onset of atrial fibrillation with the subsequent complication of embolization. In addition, these patients are susceptible to endocarditis. A study of the survival of patients with chronic regurgitation was performed using randomly selected patients. The study revealed that 80% of the patients were alive 5 years later, and 60% were alive after 10 years.
Most patients with MVP are asymptomatic. Prolapse in those older than 60 years is frequently associated with chest pain, arrhythmias, and heart failure. The prognosis of these patients is good; however, sudden death, endocarditis, and progressive regurgitation occur rarely.
When ischemic heart disease is the mechanism for regurgitation, the extent of anatomic disease and left ventricular performance are prognostic determinants. Complicating events include sudden death and myocardial infarction.
Sex
In those younger than 20 years, males are affected more often than females.
In those older than 20 years, no sexual predilection exists.
Males older than 50 years are affected more severely.
Age
Of those cases caused by prior rheumatic disease, the mean age is 36, plus or minus 6 years.
Read more HERE
Pathophysiology
Mitral regurgitation can be divided into the following 3 stages: acute, chronic compensated, and chronic decompensated.
In the acute stage, which usually occurs with a spontaneous chordae tendineae rupture secondary to myocardial infarction, a sudden volume overload occurs on an unprepared left ventricle and left atrium. The volume overload on the left ventricle increases left ventricular stroke work. Increased left ventricular filling pressures, combined with the transfer of blood from the left ventricle to the left atrium during systole, results in elevated left atrial pressures. This increased pressure is transmitted to the lungs resulting in acute pulmonary edema and dyspnea.
If the patient tolerates the acute phase, the chronic compensated phase begins. The chronic compensated phase results in eccentric left ventricular hypertrophy. The combination of increased preload and hypertrophy produces increased end-diastolic volumes, which, over time, result in left ventricular muscle dysfunction. This muscle dysfunction impairs the emptying of the ventricle during systole. Therefore, regurgitant volume and left atrial pressures increase, leading to pulmonary congestion.
Frequency
United States
Previously, chronic rheumatic heart disease was the most common cause of acquired mitral valve disease in the Western world. More recently, however, mitral valve prolapse (MVP) has become the most common cause, being responsible for 45% of cases of mitral regurgitation. MVP has been estimated to be present in 4% of the population; however, significant regurgitation in this population only occurs in those with abnormalities of the valve.
International
In areas other than the Western world, rheumatic heart disease remains the leading cause of mitral regurgitation.
Mortality/Morbidity
The prognosis of patients with mitral regurgitation depends on the underlying etiologies and the state of the left ventricular function.
Acute pulmonary edema and cardiogenic shock often complicate the course of acute regurgitation. The operative mortality in these cases approaches 80%. A patient with ruptured chordae tendineae and minimal symptoms has a much better prognosis.
With chronic regurgitation, volume overload is tolerated very well for years before symptoms of failure develop. Left atrial enlargement predisposes patients to the onset of atrial fibrillation with the subsequent complication of embolization. In addition, these patients are susceptible to endocarditis. A study of the survival of patients with chronic regurgitation was performed using randomly selected patients. The study revealed that 80% of the patients were alive 5 years later, and 60% were alive after 10 years.
Most patients with MVP are asymptomatic. Prolapse in those older than 60 years is frequently associated with chest pain, arrhythmias, and heart failure. The prognosis of these patients is good; however, sudden death, endocarditis, and progressive regurgitation occur rarely.
When ischemic heart disease is the mechanism for regurgitation, the extent of anatomic disease and left ventricular performance are prognostic determinants. Complicating events include sudden death and myocardial infarction.
Sex
In those younger than 20 years, males are affected more often than females.
In those older than 20 years, no sexual predilection exists.
Males older than 50 years are affected more severely.
Age
Of those cases caused by prior rheumatic disease, the mean age is 36, plus or minus 6 years.
Read more HERE
Friday 6 June 2008
Shock, Hypovolemic
Hypovolemic shock refers to a medical or surgical condition in which rapid fluid loss results in multiple organ failure due to inadequate circulating volume and subsequent inadequate perfusion. Most often, hypovolemic shock is secondary to rapid blood loss (hemorrhagic shock).
Acute external blood loss secondary to penetrating trauma and severe GI bleeding disorders are 2 common causes of hemorrhagic shock. Hemorrhagic shock can also result from significant acute internal blood loss into the thoracic and abdominal cavities.
Two common causes of rapid internal blood loss are solid organ injury and rupture of an abdominal aortic aneurysm. Hypovolemic shock can result from significant fluid (other than blood) loss. Two examples of hypovolemic shock secondary to fluid loss include refractory gastroenteritis and extensive burns. The remainder of this article concentrates mainly on hypovolemic shock secondary to blood loss and the controversies surrounding the treatment of this condition. The reader is referred to other articles for discussions of the pathophysiology and treatment for hypovolemic shock resulting from losses of fluid other than blood.
The many life-threatening injuries experienced during the wars of the 1900s have significantly affected the development of the principles of hemorrhagic shock resuscitation. During World War I, W.B. Cannon recommended delaying fluid resuscitation until the cause of the hemorrhagic shock was repaired surgically. Crystalloids and blood were used extensively during World War II for the treatment of patients in unstable conditions. Experience from the Korean and Vietnam wars revealed that volume resuscitation and early surgical intervention were paramount for surviving traumatic injuries resulting in hemorrhagic shock. These and other principles helped in the development of present guidelines for the treatment of traumatic hemorrhagic shock. However, recent investigators have questioned these guidelines, and today, controversies exist concerning the optimal treatment of hemorrhagic shock.For more information, see Medscape's Trauma Resource Center.
Pathophysiology
The human body responds to acute hemorrhage by activating the following major physiologic systems: the hematologic, cardiovascular, renal, and neuroendocrine systems.
The hematologic system responds to an acute severe blood loss by activating the coagulation cascade and contracting the bleeding vessels (by means of local thromboxane A2 release). In addition, platelets are activated (also by means of local thromboxane A2 release) and form an immature clot on the bleeding source. The damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot. Approximately 24 hours are needed for complete clot fibrination and mature formation.
The cardiovascular system initially responds to hypovolemic shock by increasing the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels. This response occurs secondary to an increased release of norepinephrine and decreased baseline vagal tone (regulated by the baroreceptors in the carotid arch, aortic arch, left atrium, and pulmonary vessels). The cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract.
The renal system responds to hemorrhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I, which subsequently is converted to angiotensin II by the lungs and liver. Angiotensin II has 2 main effects, both of which help to reverse hemorrhagic shock, vasoconstriction of arteriolar smooth muscle, and stimulation of aldosterone secretion by the adrenal cortex. Aldosterone is responsible for active sodium reabsorption and subsequent water conservation.
The neuroendocrine system responds to hemorrhagic shock by causing an increase in circulating antidiuretic hormone (ADH). ADH is released from the posterior pituitary gland in response to a decrease in BP (as detected by baroreceptors) and a decrease in the sodium concentration (as detected by osmoreceptors). ADH indirectly leads to an increased reabsorption of water and salt (NaCl) by the distal tubule, the collecting ducts, and the loop of Henle.
The pathophysiology of hypovolemic shock is much more involved than what was just listed. To explore the pathophysiology in more detail, references for further reading are provided in the bibliography. These intricate mechanisms list above are effective in maintaining vital organ perfusion in severe blood loss. Without fluid and blood resuscitation and/or correction of the underlying pathology causing the hemorrhage, cardiac perfusion eventually diminishes, and multiple organ failure soon follows.
Read more HERE
Acute external blood loss secondary to penetrating trauma and severe GI bleeding disorders are 2 common causes of hemorrhagic shock. Hemorrhagic shock can also result from significant acute internal blood loss into the thoracic and abdominal cavities.
Two common causes of rapid internal blood loss are solid organ injury and rupture of an abdominal aortic aneurysm. Hypovolemic shock can result from significant fluid (other than blood) loss. Two examples of hypovolemic shock secondary to fluid loss include refractory gastroenteritis and extensive burns. The remainder of this article concentrates mainly on hypovolemic shock secondary to blood loss and the controversies surrounding the treatment of this condition. The reader is referred to other articles for discussions of the pathophysiology and treatment for hypovolemic shock resulting from losses of fluid other than blood.
The many life-threatening injuries experienced during the wars of the 1900s have significantly affected the development of the principles of hemorrhagic shock resuscitation. During World War I, W.B. Cannon recommended delaying fluid resuscitation until the cause of the hemorrhagic shock was repaired surgically. Crystalloids and blood were used extensively during World War II for the treatment of patients in unstable conditions. Experience from the Korean and Vietnam wars revealed that volume resuscitation and early surgical intervention were paramount for surviving traumatic injuries resulting in hemorrhagic shock. These and other principles helped in the development of present guidelines for the treatment of traumatic hemorrhagic shock. However, recent investigators have questioned these guidelines, and today, controversies exist concerning the optimal treatment of hemorrhagic shock.For more information, see Medscape's Trauma Resource Center.
Pathophysiology
The human body responds to acute hemorrhage by activating the following major physiologic systems: the hematologic, cardiovascular, renal, and neuroendocrine systems.
The hematologic system responds to an acute severe blood loss by activating the coagulation cascade and contracting the bleeding vessels (by means of local thromboxane A2 release). In addition, platelets are activated (also by means of local thromboxane A2 release) and form an immature clot on the bleeding source. The damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot. Approximately 24 hours are needed for complete clot fibrination and mature formation.
The cardiovascular system initially responds to hypovolemic shock by increasing the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels. This response occurs secondary to an increased release of norepinephrine and decreased baseline vagal tone (regulated by the baroreceptors in the carotid arch, aortic arch, left atrium, and pulmonary vessels). The cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract.
The renal system responds to hemorrhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus. Renin converts angiotensinogen to angiotensin I, which subsequently is converted to angiotensin II by the lungs and liver. Angiotensin II has 2 main effects, both of which help to reverse hemorrhagic shock, vasoconstriction of arteriolar smooth muscle, and stimulation of aldosterone secretion by the adrenal cortex. Aldosterone is responsible for active sodium reabsorption and subsequent water conservation.
The neuroendocrine system responds to hemorrhagic shock by causing an increase in circulating antidiuretic hormone (ADH). ADH is released from the posterior pituitary gland in response to a decrease in BP (as detected by baroreceptors) and a decrease in the sodium concentration (as detected by osmoreceptors). ADH indirectly leads to an increased reabsorption of water and salt (NaCl) by the distal tubule, the collecting ducts, and the loop of Henle.
The pathophysiology of hypovolemic shock is much more involved than what was just listed. To explore the pathophysiology in more detail, references for further reading are provided in the bibliography. These intricate mechanisms list above are effective in maintaining vital organ perfusion in severe blood loss. Without fluid and blood resuscitation and/or correction of the underlying pathology causing the hemorrhage, cardiac perfusion eventually diminishes, and multiple organ failure soon follows.
Read more HERE
Thursday 5 June 2008
Anaphylaxis
Anaphylaxis refers to a severe allergic reaction in which prominent dermal and systemic signs and symptoms manifest. The full-blown syndrome includes urticaria (hives) and/or angioedema with hypotension and bronchospasm. The classic form, described in 1902, involves prior sensitization to an allergen with later re-exposure, producing symptoms via an immunologic mechanism. An anaphylactoid reaction produces a very similar clinical syndrome but is not immune-mediated. Treatment for both conditions is similar, and this article uses the term anaphylaxis to refer to both conditions unless otherwise specified.
Pathophysiology
Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an inciting substance. These effects are produced by the release of mediators, which include histamine, leukotriene C4, prostaglandin D2, and tryptase.
In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage. Histamine release in skin causes urticarial skin lesions.
The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other types of exposures also have been implicated. Anaphylaxis also may be idiopathic.
Frequency
United States
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. Some authors consider up to 15% of the US population "at risk" for anaphylaxis. The frequency of anaphylaxis is increasing and this has been attributed to the increased number of potential allergens to which people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the US.
International
Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of the greater biodiversity in these areas.
Mortality/Morbidity
Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions to Hymenoptera stings are reported each year in the United States but this is considered to be an underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less severe reactions.
Race
Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and socioeconomic differences may influence exposure rates.
Sex
No major differences have been reported in the incidence and prevalence of anaphylactic reactions between men and women.
Age
Anaphylaxis occurs in all age groups. While prior exposure is essential for the development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus, patients may react to a first exposure to an antibiotic or insect sting. Adults are exposed to more potential allergens than are pediatric patients. The elderly have the greatest risk of mortality from anaphylaxis due to the presence of preexisting disease.
Read more HERE
Pathophysiology
Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an inciting substance. These effects are produced by the release of mediators, which include histamine, leukotriene C4, prostaglandin D2, and tryptase.
In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage. Histamine release in skin causes urticarial skin lesions.
The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other types of exposures also have been implicated. Anaphylaxis also may be idiopathic.
Frequency
United States
The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. Some authors consider up to 15% of the US population "at risk" for anaphylaxis. The frequency of anaphylaxis is increasing and this has been attributed to the increased number of potential allergens to which people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the US.
International
Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of the greater biodiversity in these areas.
Mortality/Morbidity
Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions to Hymenoptera stings are reported each year in the United States but this is considered to be an underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less severe reactions.
Race
Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and socioeconomic differences may influence exposure rates.
Sex
No major differences have been reported in the incidence and prevalence of anaphylactic reactions between men and women.
Age
Anaphylaxis occurs in all age groups. While prior exposure is essential for the development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus, patients may react to a first exposure to an antibiotic or insect sting. Adults are exposed to more potential allergens than are pediatric patients. The elderly have the greatest risk of mortality from anaphylaxis due to the presence of preexisting disease.
Read more HERE
Wednesday 4 June 2008
Stevens-Johnson Syndrome
Background
First described in 1922, Stevens-Johnson syndrome (SJS) is an immune-complex–mediated hypersensitivity complex that is a severe expression of erythema multiforme. It is known by some as erythema multiforme major, but disagreement exists in the literature. Most authors and experts consider SJS and toxic epidermal necrolysis (TEN) different manifestations of the same disease. For that reason, many refer to the entity as SJS/TEN. SJS typically involves the skin and the mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. SJS is a serious systemic disorder with the potential for severe morbidity and even death. Missed diagnosis is common.
Although several classification schemes have been reported, the simplest breaks the disease down as follows:1
SJS - A "minor form of TEN," with less than 10% body surface area (BSA) detachment
Overlapping SJS/TEN - Detachment of 10-30% BSA
TEN - Detachment of more than 30% BSA
Pathophysiology
SJS is an immune-complex–mediated hypersensitivity disorder that may be caused by many drugs, viral infections, and malignancies. Cocaine recently has been added to the list of drugs capable of producing the syndrome. In up to half of cases, no specific etiology has been identified.
Pathologically, cell death results causing separation of the epidermis from the dermis. The death receptor, Fas, and its ligand, FasL, have been linked to the process. Some have also linked inflammatory cytokines to the pathogenesis.
Frequency
United States
Cases tend to have a propensity for the early spring and winter.
International
SJS occurs with a worldwide distribution similar in etiology and occurrence to that in the United States.
Mortality/Morbidity
Mortality is determined primarily by the extent of skin sloughing. When BSA sloughing is less than 10%, the mortality rate is approximately 1-5%. However, when more than 30% BSA sloughing is present, the mortality rate is between 25% and 35%.
See SCORTEN for a more complete discussion of severity of illness and mortality.
Lesions may continue to erupt in crops for as long as 2-3 weeks. Mucosal pseudomembrane formation may lead to mucosal scarring and loss of function of the involved organ system. Esophageal strictures may occur when extensive involvement of the esophagus exists. Mucosal shedding in the tracheobronchial tree may lead to respiratory failure.
Ocular sequelae may include corneal ulceration and anterior uveitis. Blindness may develop secondary to severe keratitis or panophthalmitis in 3-10% of patients. Vaginal stenosis and penile scarring have been reported. Renal complications are rare.
Race
A Caucasian predominance has been reported.
Sex
The male-to-female ratio is 2:1.
Age
Most patients are in the second to fourth decade of their lives; however, cases have been reported in children as young as 3 months.
Read more HERE
First described in 1922, Stevens-Johnson syndrome (SJS) is an immune-complex–mediated hypersensitivity complex that is a severe expression of erythema multiforme. It is known by some as erythema multiforme major, but disagreement exists in the literature. Most authors and experts consider SJS and toxic epidermal necrolysis (TEN) different manifestations of the same disease. For that reason, many refer to the entity as SJS/TEN. SJS typically involves the skin and the mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. SJS is a serious systemic disorder with the potential for severe morbidity and even death. Missed diagnosis is common.
Although several classification schemes have been reported, the simplest breaks the disease down as follows:1
SJS - A "minor form of TEN," with less than 10% body surface area (BSA) detachment
Overlapping SJS/TEN - Detachment of 10-30% BSA
TEN - Detachment of more than 30% BSA
Pathophysiology
SJS is an immune-complex–mediated hypersensitivity disorder that may be caused by many drugs, viral infections, and malignancies. Cocaine recently has been added to the list of drugs capable of producing the syndrome. In up to half of cases, no specific etiology has been identified.
Pathologically, cell death results causing separation of the epidermis from the dermis. The death receptor, Fas, and its ligand, FasL, have been linked to the process. Some have also linked inflammatory cytokines to the pathogenesis.
Frequency
United States
Cases tend to have a propensity for the early spring and winter.
International
SJS occurs with a worldwide distribution similar in etiology and occurrence to that in the United States.
Mortality/Morbidity
Mortality is determined primarily by the extent of skin sloughing. When BSA sloughing is less than 10%, the mortality rate is approximately 1-5%. However, when more than 30% BSA sloughing is present, the mortality rate is between 25% and 35%.
See SCORTEN for a more complete discussion of severity of illness and mortality.
Lesions may continue to erupt in crops for as long as 2-3 weeks. Mucosal pseudomembrane formation may lead to mucosal scarring and loss of function of the involved organ system. Esophageal strictures may occur when extensive involvement of the esophagus exists. Mucosal shedding in the tracheobronchial tree may lead to respiratory failure.
Ocular sequelae may include corneal ulceration and anterior uveitis. Blindness may develop secondary to severe keratitis or panophthalmitis in 3-10% of patients. Vaginal stenosis and penile scarring have been reported. Renal complications are rare.
Race
A Caucasian predominance has been reported.
Sex
The male-to-female ratio is 2:1.
Age
Most patients are in the second to fourth decade of their lives; however, cases have been reported in children as young as 3 months.
Read more HERE
Tuesday 3 June 2008
Dysmenorrhea
Dysmenorrhea refers to the syndrome of painful menstruation. Primary dysmenorrhea occurs in the absence of pelvic pathology, whereas secondary dysmenorrhea results from identifiable organic diseases, most typically endometriosis, uterine fibroids, uterine adenomyosis, or chronic pelvic inflammatory disease. The prevalence of dysmenorrhea is estimated to be between 45 and 95% among reproductive-aged women. Although not life threatening, dysmenorrhea can be debilitating and psychologically taxing for many women and is one of the leading causes of absenteeism from work and school.
Pathophysiology
Historical attitudes toward menstrual pain were often dismissive. Pain was often attributed to women's emotional or psychological states, misconceptions about sex, and unhealthy maternal relations. Research has now established concrete physiologic explanations for dysmenorrhea, which discredit these prior theories.
Primary dysmenorrhea usually begins within the first 6-12 months after menarche once a regular ovulatory cycle has been established. During menstruation, sloughing endometrial cells release prostaglandins, which cause uterine ischemia through myometrial contraction and vasoconstriction. Elevated levels of prostaglandins have been measured in the menstrual fluid of women with severe dysmenorrhea. These levels are especially high during the first 2 days of menstruation. Vasopressin may also play a similar role.
Secondary dysmenorrhea may present at any time after menarche, but most commonly arises when a woman is in her 20s or 30s, after years of normal, relatively painless cycles. Elevated prostaglandins may also play a role in secondary dysmenorrhea, but, by definition, concomitant pelvic pathology must also be present. Common causes include endometriosis, leiomyomata (fibroids), adenomyosis, endometrial polyps, chronic pelvic inflammatory disease, and IUD use.
Frequency
United States
The prevalence of dysmenorrhea is estimated at 45-90%. This wide range can be explained by an assumed underreporting of symptoms. Many women self-medicate at home and never seek medical attention for their pain. As mentioned above, dysmenorrhea is responsible for significant absenteeism from work and school; 13-51% of women have been absent at least once, and 5-14% are repeatedly absent.
International
One longitudinal study from Sweden reported dysmenorrhea in 90% of women younger than 19 years and in 67% of women aged 24 years (French, 2005).
Mortality/Morbidity
Dysmenorrhea itself is not life threatening, but it can have a profoundly negative impact on a woman's day-to-day life. In addition to missing work or school, she may be unable to participate in sports or other activities, compounding the emotional distress brought on by the pain.
Race
No significant difference is apparent in the prevalence of dysmenorrhea among different populations.
Sex
Despite prevailing trends toward equality in the sexes, men are not yet known to experience dysmenorrhea.
Age
See Frequency above.
Read more HERE
Pathophysiology
Historical attitudes toward menstrual pain were often dismissive. Pain was often attributed to women's emotional or psychological states, misconceptions about sex, and unhealthy maternal relations. Research has now established concrete physiologic explanations for dysmenorrhea, which discredit these prior theories.
Primary dysmenorrhea usually begins within the first 6-12 months after menarche once a regular ovulatory cycle has been established. During menstruation, sloughing endometrial cells release prostaglandins, which cause uterine ischemia through myometrial contraction and vasoconstriction. Elevated levels of prostaglandins have been measured in the menstrual fluid of women with severe dysmenorrhea. These levels are especially high during the first 2 days of menstruation. Vasopressin may also play a similar role.
Secondary dysmenorrhea may present at any time after menarche, but most commonly arises when a woman is in her 20s or 30s, after years of normal, relatively painless cycles. Elevated prostaglandins may also play a role in secondary dysmenorrhea, but, by definition, concomitant pelvic pathology must also be present. Common causes include endometriosis, leiomyomata (fibroids), adenomyosis, endometrial polyps, chronic pelvic inflammatory disease, and IUD use.
Frequency
United States
The prevalence of dysmenorrhea is estimated at 45-90%. This wide range can be explained by an assumed underreporting of symptoms. Many women self-medicate at home and never seek medical attention for their pain. As mentioned above, dysmenorrhea is responsible for significant absenteeism from work and school; 13-51% of women have been absent at least once, and 5-14% are repeatedly absent.
International
One longitudinal study from Sweden reported dysmenorrhea in 90% of women younger than 19 years and in 67% of women aged 24 years (French, 2005).
Mortality/Morbidity
Dysmenorrhea itself is not life threatening, but it can have a profoundly negative impact on a woman's day-to-day life. In addition to missing work or school, she may be unable to participate in sports or other activities, compounding the emotional distress brought on by the pain.
Race
No significant difference is apparent in the prevalence of dysmenorrhea among different populations.
Sex
Despite prevailing trends toward equality in the sexes, men are not yet known to experience dysmenorrhea.
Age
See Frequency above.
Read more HERE
Monday 2 June 2008
Rh Incompatibility
The Rh factor (ie, Rhesus factor) is a red blood cell surface antigen that was named after the monkeys in which it was first discovered. Rh incompatibility, also known as Rh disease, is a condition that occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells, leading to the development of Rh antibodies.
Rh incompatibility can occur by 2 main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery. Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion. In part, this is the reason that blood banks prefer using blood type "O negative" or "type O, Rh negative," as the universal donor type in emergency situations when there is no time to type and crossmatch blood.
The most common cause of Rh incompatibility is exposure from an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery. As a consequence, blood from the fetal circulation may leak into the maternal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen.
Once produced, maternal Rh immunoglobulin G (IgG) antibodies may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. Although the Rh blood group systems consist of several antigens (eg, D, C, c, E, e), the D antigen is the most immunogenic; therefore, it most commonly is involved in Rh incompatibility.
Pathophysiology
The amount of fetal blood necessary to produce Rh incompatibility varies. In one study, less than 1 mL of Rh-positive blood was shown to sensitize volunteers with Rh-negative blood. Conversely, other studies have suggested that 30% of persons with Rh-negative blood never develop Rh incompatibility, even when challenged with large volumes of Rh-positive blood. Once sensitized, it takes approximately one month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation. In 90% of cases, sensitization occurs during delivery. Therefore, most firstborn infants with Rh-positive blood type are not affected because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response.
The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rh-positive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia.
Risk of sensitization depends largely upon the following 3 factors:
Volume of transplacental hemorrhage
Extent of the maternal immune response
Concurrent presence of ABO incompatibility
The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother's serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent. Fortunately, ABO incompatibility usually does not cause serious sequela.
Rh incompatibility is only of medical concern for females who are pregnant or plan to have children in the future. Rh-positive antibodies circulating in the bloodstream of an Rh-negative woman otherwise have no adverse effects.
Frequency
United States
Only 15% of the population lack the Rh erythrocyte surface antigen and are considered Rh-negative. The vast majority (85%) of individuals are considered Rh positive. Rh sensitization occurs in approximately 1 per 1000 births to women who are Rh negative. The Southwest United States has an incidence approximately 1.5 times the national average, which likely is caused by immigration factors and limited access to medical care since blood typing is a routine part of prenatal care. Even so, only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells ever develop Rh antibodies.
Mortality/Morbidity
During the course of Rh incompatibility, the fetus is primarily affected. The binding of maternal Rh antibodies produced after sensitization with fetal Rh-positive erythrocytes results in fetal autoimmune hemolysis. As a consequence, large amounts of bilirubin are produced from the breakdown of fetal hemoglobin and are transferred via the placenta to the mother where they are subsequently conjugated and excreted by the mother. However, once delivered, low levels of glucuronyl transferase in the infant preclude the conjugation of large amounts of bilirubin and may result in dangerously elevated levels of serum bilirubin and severe jaundice.
Mildly affected infants may have little or no anemia and may exhibit only hyperbilirubinemia secondary to the continuing hemolytic effect of Rh antibodies that have crossed the placenta.
Moderately affected infants may have a combination of anemia and hyperbilirubinemia/jaundice.
In severe cases of fetal hyperbilirubinemia, kernicterus develops. Kernicterus is a neurologic syndrome caused by deposition of bilirubin into central nervous system tissues. Kernicterus usually occurs several days after delivery and is characterized by loss of the Moro (ie, startle) reflex, posturing, poor feeding, inactivity, a bulging fontanelle, a high-pitched shrill cry, and seizures. Infants who survive kernicterus may go on to develop hypotonia, hearing loss, and mental retardation.
Another serious life-threatening condition observed in infants affected by Rh incompatibility is erythroblastosis fetalis, which is characterized by severe hemolytic anemia and jaundice. The most severe form of erythroblastosis fetalis is hydrops fetalis, which is characterized by high output cardiac failure, edema, ascites, pericardial effusion, and extramedullary hematopoiesis. Newborns with hydrops fetalis are extremely pale with hematocrits usually less than 5. Hydrops fetalis often results in death of the infant shortly before or after delivery and requires an emergent exchange transfusion by a neonatologist if there is to be any chance of infant survival.
Race
Approximately 15-20% of Caucasians, as opposed to 5-10% of African Americans, have the Rh-negative blood type.
Among individuals of Chinese and American Indian descent, the incidence of Rh-negative blood type is less than 5%.
CLINICAL
History of prior blood transfusion
Rh blood type of the mother
Rh blood type of the father (55% of Rh-positive men are genetically heterozygous for the Rh antigen and, therefore, produce Rh-negative offspring when mating with Rh-negative women 50% of the time.)
Previous pregnancies, including spontaneous and elective abortions
Previous administration of Rh IgG (RhoGAM)
Mechanism of injury in cases of maternal trauma during pregnancy
Presence of vaginal bleeding and/or amniotic discharge
Previous invasive obstetric procedures, such as amniocentesis, cordocentesis, chorionic villous sampling, or ectopic pregnancy
Note that a large fetal-maternal hemorrhage may occur without symptoms and with little or no evidence of trauma. Therefore, a high index of suspicion is warranted and a low threshold for treatment is indicated.
Physical
Evaluation of the vital signs and primary survey of the airway and cardiovascular system are indicated to ensure maternal stability.
A thorough pelvic examination is required.
In situations in which abdominal and/or pelvic trauma is a consideration, inspect for evidence of bruising that may suggest the possibility of significant fetomaternal hemorrhage.
When an infant with an Rh-negative mother is delivered in the emergency department, a thorough physical examination of the infant must be performed after initial stabilization, and a neonatologist must be consulted immediately.
Physical findings may vary from mild jaundice to extreme pallor and anemia with hydrops fetalis.
Causes
Factors that influence an Rh-negative pregnant female's chances of developing Rh incompatibility include the following:
Ectopic pregnancy
Placenta previa
Placental abruption
Abdominal/pelvic trauma
In utero fetal death
Any invasive obstetric procedure (eg, amniocentesis)
Lack of prenatal care
Spontaneous abortion
DIFFERENTIALS
Other Problems to be Considered
ABO incompatibility Autoimmune hemolytic anemia Microangiopathic hemolytic anemia Spherocytosis Hereditary enzyme deficiencies Alpha thalassemia Chronic fetomaternal hemorrhage Twin-twin transfusion Erythroblastosis fetalis Hydrops fetalis
Read more HERE
Rh incompatibility can occur by 2 main mechanisms. The most common type occurs when an Rh-negative pregnant mother is exposed to Rh-positive fetal red blood cells secondary to fetomaternal hemorrhage during the course of pregnancy from spontaneous or induced abortion, trauma, invasive obstetric procedures, or normal delivery. Rh incompatibility can also occur when an Rh-negative female receives an Rh-positive blood transfusion. In part, this is the reason that blood banks prefer using blood type "O negative" or "type O, Rh negative," as the universal donor type in emergency situations when there is no time to type and crossmatch blood.
The most common cause of Rh incompatibility is exposure from an Rh-negative mother by Rh-positive fetal blood during pregnancy or delivery. As a consequence, blood from the fetal circulation may leak into the maternal circulation, and, after a significant exposure, sensitization occurs leading to maternal antibody production against the foreign Rh antigen.
Once produced, maternal Rh immunoglobulin G (IgG) antibodies may cross freely from the placenta to the fetal circulation, where they form antigen-antibody complexes with Rh-positive fetal erythrocytes and eventually are destroyed, resulting in a fetal alloimmune-induced hemolytic anemia. Although the Rh blood group systems consist of several antigens (eg, D, C, c, E, e), the D antigen is the most immunogenic; therefore, it most commonly is involved in Rh incompatibility.
Pathophysiology
The amount of fetal blood necessary to produce Rh incompatibility varies. In one study, less than 1 mL of Rh-positive blood was shown to sensitize volunteers with Rh-negative blood. Conversely, other studies have suggested that 30% of persons with Rh-negative blood never develop Rh incompatibility, even when challenged with large volumes of Rh-positive blood. Once sensitized, it takes approximately one month for Rh antibodies in the maternal circulation to equilibrate in the fetal circulation. In 90% of cases, sensitization occurs during delivery. Therefore, most firstborn infants with Rh-positive blood type are not affected because the short period from first exposure of Rh-positive fetal erythrocytes to the birth of the infant is insufficient to produce a significant maternal IgG antibody response.
The risk and severity of sensitization response increases with each subsequent pregnancy involving a fetus with Rh-positive blood. In women who are prone to Rh incompatibility, the second pregnancy with an Rh-positive fetus often produces a mildly anemic infant, whereas succeeding pregnancies produce more seriously affected infants who ultimately may die in utero from massive antibody-induced hemolytic anemia.
Risk of sensitization depends largely upon the following 3 factors:
Volume of transplacental hemorrhage
Extent of the maternal immune response
Concurrent presence of ABO incompatibility
The incidence of Rh incompatibility in the Rh-negative mother who is also ABO incompatible is reduced dramatically to 1-2% and is believed to occur because the mother's serum contains antibodies against the ABO blood group of the fetus. The few fetal red blood cells that are mixed with the maternal circulation are destroyed before Rh sensitization can proceed to a significant extent. Fortunately, ABO incompatibility usually does not cause serious sequela.
Rh incompatibility is only of medical concern for females who are pregnant or plan to have children in the future. Rh-positive antibodies circulating in the bloodstream of an Rh-negative woman otherwise have no adverse effects.
Frequency
United States
Only 15% of the population lack the Rh erythrocyte surface antigen and are considered Rh-negative. The vast majority (85%) of individuals are considered Rh positive. Rh sensitization occurs in approximately 1 per 1000 births to women who are Rh negative. The Southwest United States has an incidence approximately 1.5 times the national average, which likely is caused by immigration factors and limited access to medical care since blood typing is a routine part of prenatal care. Even so, only 17% of pregnant women with Rh-negative blood who are exposed to Rh-positive fetal blood cells ever develop Rh antibodies.
Mortality/Morbidity
During the course of Rh incompatibility, the fetus is primarily affected. The binding of maternal Rh antibodies produced after sensitization with fetal Rh-positive erythrocytes results in fetal autoimmune hemolysis. As a consequence, large amounts of bilirubin are produced from the breakdown of fetal hemoglobin and are transferred via the placenta to the mother where they are subsequently conjugated and excreted by the mother. However, once delivered, low levels of glucuronyl transferase in the infant preclude the conjugation of large amounts of bilirubin and may result in dangerously elevated levels of serum bilirubin and severe jaundice.
Mildly affected infants may have little or no anemia and may exhibit only hyperbilirubinemia secondary to the continuing hemolytic effect of Rh antibodies that have crossed the placenta.
Moderately affected infants may have a combination of anemia and hyperbilirubinemia/jaundice.
In severe cases of fetal hyperbilirubinemia, kernicterus develops. Kernicterus is a neurologic syndrome caused by deposition of bilirubin into central nervous system tissues. Kernicterus usually occurs several days after delivery and is characterized by loss of the Moro (ie, startle) reflex, posturing, poor feeding, inactivity, a bulging fontanelle, a high-pitched shrill cry, and seizures. Infants who survive kernicterus may go on to develop hypotonia, hearing loss, and mental retardation.
Another serious life-threatening condition observed in infants affected by Rh incompatibility is erythroblastosis fetalis, which is characterized by severe hemolytic anemia and jaundice. The most severe form of erythroblastosis fetalis is hydrops fetalis, which is characterized by high output cardiac failure, edema, ascites, pericardial effusion, and extramedullary hematopoiesis. Newborns with hydrops fetalis are extremely pale with hematocrits usually less than 5. Hydrops fetalis often results in death of the infant shortly before or after delivery and requires an emergent exchange transfusion by a neonatologist if there is to be any chance of infant survival.
Race
Approximately 15-20% of Caucasians, as opposed to 5-10% of African Americans, have the Rh-negative blood type.
Among individuals of Chinese and American Indian descent, the incidence of Rh-negative blood type is less than 5%.
CLINICAL
History of prior blood transfusion
Rh blood type of the mother
Rh blood type of the father (55% of Rh-positive men are genetically heterozygous for the Rh antigen and, therefore, produce Rh-negative offspring when mating with Rh-negative women 50% of the time.)
Previous pregnancies, including spontaneous and elective abortions
Previous administration of Rh IgG (RhoGAM)
Mechanism of injury in cases of maternal trauma during pregnancy
Presence of vaginal bleeding and/or amniotic discharge
Previous invasive obstetric procedures, such as amniocentesis, cordocentesis, chorionic villous sampling, or ectopic pregnancy
Note that a large fetal-maternal hemorrhage may occur without symptoms and with little or no evidence of trauma. Therefore, a high index of suspicion is warranted and a low threshold for treatment is indicated.
Physical
Evaluation of the vital signs and primary survey of the airway and cardiovascular system are indicated to ensure maternal stability.
A thorough pelvic examination is required.
In situations in which abdominal and/or pelvic trauma is a consideration, inspect for evidence of bruising that may suggest the possibility of significant fetomaternal hemorrhage.
When an infant with an Rh-negative mother is delivered in the emergency department, a thorough physical examination of the infant must be performed after initial stabilization, and a neonatologist must be consulted immediately.
Physical findings may vary from mild jaundice to extreme pallor and anemia with hydrops fetalis.
Causes
Factors that influence an Rh-negative pregnant female's chances of developing Rh incompatibility include the following:
Ectopic pregnancy
Placenta previa
Placental abruption
Abdominal/pelvic trauma
In utero fetal death
Any invasive obstetric procedure (eg, amniocentesis)
Lack of prenatal care
Spontaneous abortion
DIFFERENTIALS
Other Problems to be Considered
ABO incompatibility Autoimmune hemolytic anemia Microangiopathic hemolytic anemia Spherocytosis Hereditary enzyme deficiencies Alpha thalassemia Chronic fetomaternal hemorrhage Twin-twin transfusion Erythroblastosis fetalis Hydrops fetalis
Read more HERE
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